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PubMed1997

Dependence of the adaptive immune response on innate immunity: some questions answered but new paradoxes emerge.

Recently a new model of vertebrate immunity has been gaining popularity. In this new model it is hypothesized that activation of innate immunity is a prerequisite for an adaptive immune response to an antigen. Following activation the innate system induces key costimulator molecules on APC, which are essential for antigen-driven clonal expansion of T and B cells. The model largely explains the need for adjuvants in the induction of adaptive immunity, provides a possible mechanism for the immune system to perceive the biological nature of a pathogen and thereby produce the most effective immune response, and transfers much of the onus of self-non-self discrimination from the adaptive to the innate immune system. In the present article we highlight two paradoxes raised by the new model. First, by linking adaptive immunity to innate recognition the immune system is unable to take full advantage of the genetic diversity of T and B cell antigen receptors. Thus, the ability of the immune system to combat a pathogen is totally dependent on the efficiency of recognition by the innate system and, therefore, the germ-line mutation rate of the genes involved in the innate response. Second, if signals from the innate system induce costimulatory molecules on APC, then one would expect the accidental clonal expansion of many autoreactive T and B cells. We suggest that one means of resolving the first paradox is to propose that the major reason for the evolution of adaptive immunity was to provide, via immunological memory, resistance to reinfection, rather than simply to combat the primary infection by the pathogen. In the case of autoreactivity we suggest that autodestruction is prevented by immune responses being tightly regulated at the effector T cell level. Finally, we argue that the two paradoxes, rather than undermining the new model of immunity, highlight our lack of understanding of key elements of the vertebrate immune system.

Adaptation, Physiological↗
PubMed2003

Analysis of differential immune responses induced by innate and adaptive immunity following transplantation.

The roles of innate and adaptive immunity in allograft rejection remain incompletely understood. Previous studies analysing lymphocyte deficient or syngeneic graft recipients have identified subsets of inflammatory chemokines and cytokines induced by antigen independent mechanisms. In the current study, we analysed a panel of 60 inflammatory parameters including serum cytokines, intragraft chemokines and cytokines, receptors, and cellular markers. Our results confirmed the up-regulation of a subset of markers by innate mechanisms and also identified a subset of parameters up-regulated only in the context of an adaptive response. Thus, we successfully differentiated markers of the innate and adaptive phases of rejection. Current paradigms emphasize that innate signals can promote a subsequent adaptive response. Interestingly, in our studies, expression of the markers induced by innate mechanisms was markedly amplified in the allogeneic, but not syngeneic or lymphocyte deficient, recipients. These results suggest that inflammatory mediators can have functional overlap between the innate and adaptive responses, and that the adaptive component of the rejection process amplifies the innate response by positive feedback regulation.

Analysis of Variance↗
PubMed2002

The classical pathway is the dominant complement pathway required for innate immunity to Streptococcus pneumoniae infection in mice.

The complement system is an important component of the innate immune response to bacterial pathogens, including Streptococcus pneumoniae. The classical complement pathway is activated by antibody-antigen complexes on the bacterial surface and has been considered predominately to be an effector of the adaptive immune response, whereas the alternative and mannose-binding lectin pathways are activated directly by bacterial cell surface components and are considered effectors of the innate immune response. Recently, a role has been suggested for the classical pathway during innate immunity that is activated by natural IgM or components of the acute-phase response bound to bacterial pathogens. However, the functional importance of the classical pathway for innate immunity to S. pneumoniae and other bacterial pathogens, and its relative contribution compared with the alternative and mannose-binding lectin pathways has not been defined. By using strains of mice with genetic deficiencies of complement components and secretory IgM we have investigated the role of each complement pathway and natural IgM for innate immunity to S. pneumoniae. Our results show that the proportion of a population of S. pneumoniae bound by C3 depends mainly on the classical pathway, whereas the intensity of C3 binding depends on the alternative pathway. Furthermore, the classical pathway, partially targeted by the binding of natural IgM to bacteria, is the dominant pathway for activation of the complement system during innate immunity to S. pneumoniae, loss of which results in rapidly progressing septicemia and impaired macrophage activation. These data demonstrate the vital role of the classical pathway for innate immunity to a bacterial pathogen.

Animals↗
PubMed2006

Cytokine modulation of the innate immune response in feline immunodeficiency virus-infected cats.

BACKGROUND: In vitro data suggest that innate immune function in human immunodeficiency virus type 1-infected patients is compromised; however, in vivo studies are lacking. Feline immunodeficiency virus (FIV) infection in cats provides an excellent model to explore innate immune function in vivo. The innate response against Listeria monocytogenes is well understood, making it a useful immune probe. METHODS: Recombinant L. monocytogenes carrying eukaryotic expression plasmids for feline tumor necrosis factor (TNF)- alpha , interleukin (IL)-10, interferon (IFN)- gamma , and IL-15 were created to determine whether specific cytokines would modulate innate immune function. L. monocytogenes was delivered subcutaneously, and local lymph nodes were evaluated for size, cell subpopulations, and L. monocytogenes burden. Two months later, memory responses were evaluated by IFN- gamma enzyme-linked immunospot assay. RESULTS: FIV-positive cats had significantly less lymph-node enlargement and a greater L. monocytogenes burden than FIV-negative control cats. TNF- alpha improved listericidal activity in FIV-negative control cats but not in FIV-positive cats, whereas IL-10 modestly reduced function in FIV-negative control cats. IFN- gamma improved memory responses but not clearance of L. monocytogenes. IL-15 improved innate function in FIV-positive cats and increased the percentage of natural killer cells. CONCLUSIONS: Lentivirus infection impairs innate immune function in vivo, and IL-15 can significantly restore function. We hypothesize that altered dendritic-cell function and increased regulatory T cell activity may underlie the innate immune defect in HIV infection.

Animals↗
PubMed2006

A shared gene-expression signature in innate-like lymphocytes.

Innate and adaptive immunities are the two major arms of the immune system, which rely on distinct cell types. These cells can be distinguished not only by the source of diversity for non-self recognition, of germline or somatic origin, but also by their localization and the pattern and rates of response after encounter of antigenic triggers. In addition, subsets of lymphocytes exist whose receptors require rearrangement but result in semi-invariant structures with a high degree of self-specificity. We hypothesized that these innate-like lymphocytes might share a common gene transcription signature that relates them to classic members of the innate immune system. This relationship was first observed in agonist-induced CD8alphaalpha T cells in fetal/neonatal thymus. We then asked whether this notion could be extended to other innate-like lymphocytes, by comparison of gene expression profiles of innate-like lymphocytes and closely paired adaptive system counterparts (NKT versus CD4T, CD8alphaalphaT versus CD8alphabetaT, and B1 versus B2). A statistically significant 'innate signature' indeed was distilled. Particularly intriguing was the high representation of interferon-inducible guanosine triphophatases crucial for resistance against intracellular pathogens and of small G proteins involved in intracellular vacuole maturation and trafficking. Overall, this combined expression pattern can be designated as an innate signature among lymphocytes.

Animals↗
PubMed2007

Innate immune response to adenoviral vectors is mediated by both Toll-like receptor-dependent and -independent pathways.

Recombinant adenoviral vectors have been widely used for gene therapy applications and as vaccine vehicles for treating infectious diseases such as human immunodeficiency virus disease. The innate immune response to adenoviruses represents the most significant hurdle in clinical application of adenoviral vectors for gene therapy, but it is an attractive feature for vaccine development. How adenovirus activates innate immunity remains largely unknown. Here we showed that adenovirus elicited innate immune response through the induction of high levels of type I interferons (IFNs) by both plasmacytoid dendritic cells (pDCs) and non-pDCs such as conventional DCs and macrophages. The innate immune recognition of adenovirus by pDCs was mediated by Toll-like receptor 9 (TLR9) and was dependent on MyD88, whereas that by non-pDCs was TLR independent through cytosolic sensing of adenoviral DNA. Furthermore, type I IFNs were pivotal in innate and adaptive immune responses to adenovirus in vivo, and type I IFN blockade diminished immune responses, resulting in more stable transgene expression and reduction of inflammation. These findings indicate that adenovirus activates innate immunity by its DNA through TLR-dependent and -independent pathways in a cell type-specific fashion, and they highlight a critical role for type I IFNs in innate and adaptive immune responses to adenoviral vectors. Our results that suggest strategies to interfere with type I IFN pathway may improve the outcome of adenovirus-mediated gene therapy, whereas approaches to activate the type I IFN pathway may enhance vaccine potency.

Adenoviridae↗
PubMed2006

[Humoral and cellular responses in innate immunity].

The immune system is divided into innate and adaptive immunity. Either immunity consists of humoral and cellular responses, and immunity is maximized when both responses coordinately function. Adaptive immunity has been intensively studied, while it was only recently that we gained some understanding of innate immunity. In particular, cellular responses in innate immunity have been poorly understood compared with humoral responses. In addition, the mechanisms and roles of innate immune responses could be distinct between the organisms that possess both innate and adaptive immunity and those possessing only innate immunity. On the other hand, invading pathogenic microbes employ various strategies to inhibit the host immune system for their survival. I here summarize what needs to be known to gain a deeper understanding of the innate immune response. The readers are suggested to refer to the accompanying articles for more detailed description.

Animals↗
PubMed2006

Innate immune responses to environmental allergens.

Aero-allergens, including plant pollens, house dust mite particles, fungal spores, and mycelium fragments, are continuously inhaled and deposited on the airway mucosa. These particles and their soluble components actively interact with innate recognition systems present in the mucosal layer (e.g., surfactant proteins) and with various receptors present on a diversity of cells in the airways. Deposited particles are first removed by active transportation, the rate of which is either enhanced or inhibited by components present in the inhaled substances. Cleaning further depends on innate recognition, beginning with (a) soluble factors released into the mucosal surface layer that bind different bio-organic components; (b) innate receptors on phagocytic cells, alveolar macrophages, and dendritic monocytes; and (c) innate receptors on airway epithelial cells. Different innate receptor families (Toll-like receptors [TLRs], nucleotide-binding oligomerization domain receptors, and protein-activated receptors [PARs]) have been demonstrated on airway cells, including alveolar macrophages, monocytes, dendritic cells, and airway tissue cells (e.g., epithelial cells and mast cells). However, although the functional role of these receptors has been studied for infectious diseases, the functional role for reaction of airways to inhaled bio-organic substances, including allergens, is largely unexplored. Indirect evidence for functional interactions has come from in vivo animal studies, as well as in vitro studies with monocytes, macrophages, and epithelial cells, which have demonstrated release of cytokines and chemokines after contact with allergens such as house dust mite, cat, pollen, and fungi. Most allergens show direct activation of airway epithelial cells, suggesting a role for the innate receptors. However, the role of TLRs, PARs, and other receptors was studied for only a limited number of allergens. Current studies indicate synergistic interactions between members of the same receptor family (TLRs) as well as synergistic interactions between members of different families (TLRs, PARs, and nucleotide-binding oligomerization domain receptors), modulating responses into feed-forward or inhibitory actions. Study of these synergistic interactions and their genetic variations will provide insight regarding how the innate immune system determines the inflammatory reactions of the airways and the outcome of the T-helper-1- and T-helper-2-type responses to inhaled allergens.

Air Pollutants↗
PubMedDate not supplied

A role for innate immunity in type 1 diabetes?

Two arms of the immune system, innate and adaptive immunity, differ in their mode of immune recognition. The innate immune system recognizes a few highly conserved structures on a broad range of microorganisms. On the other hand, recognition of self or autoreactivity is generally confined to the adaptive immune response. Whilst autoimmune features are relatively common, they should be distinguished from autoimmune disease that is infrequent. Type 1 diabetes is an immune-mediated disease due to the destruction of insulin secreting cells mediated by aggressive immune responses, including activation of the adaptive immune system following genetic and environmental interaction. Hypotheses for the cause of the immune dysfunction leading to type 1 diabetes include self-reactive T-cell clones that (1) escape deletion in the thymus, (2) escape from peripheral tolerance or (3) escape from homeostatic control with an alteration in the immune balance leading to autoimmunity. Evidence, outlined in this review, raises the possibility that changes in the innate immune system could lead to autoimmunity, by either priming or promoting aggressive adaptive immune responses. Hostile microorganisms are identified by genetically determined surface receptors on innate effector cells, thereby promoting clearance of these invaders. These innate effectors include a few relatively inflexible cell populations such as monocytes/macrophages, dendritic cells (DC), natural killer (NK) cells, natural killer T (NKT) cells and gammadelta T cells. Recent studies have identified abnormalities in some of these cells both in patients with type 1 diabetes and in those at risk of the disease. However, it remains unclear whether these abnormalities in innate effector cells predispose to autoimmune disease. If they were to do so, then modulation of the innate immune system could be of therapeutic value in preventing immune-mediated diseases such as type 1 diabetes.

Animals↗
PubMed2026

Loss of XRCC1 promotes cGAS/STING mediated innate immune signaling in gastric cancer.

BACKGROUND: One of the most defining features of gastric cancer (GC) is harboring deficiency in DNA repair that subsequently contributes to carcinogenesis. The X-ray repair cross complementing 1 (XRCC1) protein is a key molecular scaffold required for efficient repair of DNA single-strand breaks (SSBs) to maintain genomic stability. However, further investigation is needed to uncover the role of XRCC1 in innate immune signaling and inflammation in GC. METHODS: We evaluated how loss of XRCC1 leads to accumulation of cytosolic DNA using immunofluorescence localization assay and measuring DNA from cytosolic extract. We applied ON-TARGETplus™ SMARTpool siRNAs to knockdown XRCC1 in gastric cell lines and examined the innate immune siganling and inflammation with and without ATM inhibitor treatment. Further, we examined Type I interferon gene expression in various gastric cancer cell lines and assessed its role in cGAS-STING signaling using RT-qPCR, RNA-Seq, and immunoblot analysis. In addition, we generated conditional knockout XRCC1 mice and characterized the innate immune signaling from stomach tissue extract using RT-qPCR, western blot. Further, the DNA damage and histological analysis was done by immunohistochemistry. RESULTS: In this work, we examined the role of XRCC1 in modulating the innate immune signaling axis via cGAS/STING pathway. We find that XRCC1 deficient gastric cancer cell lines and mouse stomach tissue shows activation of cGAS/STING signaling. Further, ATM inhibition enhances robust cGAS/STING mediate innate immune signaling and PD-L1 expression in XRCC1 deficient gastric cancer cells. CONCLUSIONS: Results from this work demonstrate that XRCC1 is essential to maintain innate immune homeostasis. Further, this work suggest that ATM inhibitors may provide a potential therapeutic strategy to enhance the PD-L1 expression that could increase the efficacy of an immune checkpoint blockade (ICB) in XRCC1 deficient or low expressing GC.

X-ray Repair Cross Complementing Protein 1↗
PubMed2006

Iron-withholding strategy in innate immunity.

The knowledge of how organisms fight infections has largely been built upon the ability of host innate immune molecules to recognize microbial determinants. Although of overwhelming importance, pathogen recognition is but only one of the facets of innate immunity. A primitive yet effective antimicrobial mechanism which operates by depriving microbial organisms of their nutrients has been brought into the forefront of innate immunity once again. Such a tactic is commonly referred to as the iron-withholding strategy of innate immunity. In this review, we introduce various vertebrate iron-binding proteins and their invertebrate homologues, so as to impress upon readers an obscured arm of innate immune defense. An excellent comprehension of the mechanics of innate immunity paves the way for the possibility that novel antimicrobial therapeutics may emerge one day to overcome the prevalent antibiotic resistance in bacteria.

Animals↗
PubMed2005

Role for innate immunity in rheumatoid arthritis.

Innate immunity is the first line of defense against pathogenic microorganisms (bacteria, viruses, fungi, and parasites). After a long period of neglect, innate immunity is again recognized as a key mechanism not only in preventing invasion of the body by microorganisms, but also in contributing to the pathogenesis of autoimmune and inflammatory diseases by deviating the immune response or promoting the emergence of a regulatory response. The many factors involved in innate immunity often act in parallel or in alternation to generate adaptive immune responses. Innate immune responses are specific for groups of molecules or macromolecules found in components of microorganisms, usually the cell wall. The cellular and protein effectors of innate immunity are found in the rheumatoid synovium, and an increasing body of evidence indicates that they are directly involved in joint inflammation and in destruction of the joint cartilage and bone. In addition, they may have regulatory effects on inflammation and immunity. Whether innate immune mechanisms are causes or consequences of inflammation, and whether they regulate or amplify adaptive immune responses, they constitute a target of choice for new antiinflammatory and immunoregulating treatment strategies.

Animals↗
PubMed2005

Evaluation of polyethylene glycol modification of first-generation and helper-dependent adenoviral vectors to reduce innate immune responses.

Adenoviruses are robust gene delivery vectors in vivo, but are limited by their propensity to provoke strong innate and adaptive responses. Previous work has demonstrated that polyethylene glycol (PEG) modification of adenovirus can protect the vectors from preexisting and adaptive immune responses by reducing protein-protein interactions. To test whether PEGylation can reduce innate immune responses to adenovirus by reducing their interactions with immune cells, first-generation (FG-Ad) and helper-dependent (HD-Ad) Ad5 vectors were PEGylated with SPA-PEG and tested in vitro and in vivo. We demonstrate that increasing PEGylation ablated in vitro transduction, but surprisingly had no negative effect on the level or distribution of in vivo gene delivery. This poor in vitro transduction could be rescued in part by physically forcing the PEGylated vectors onto cells, suggesting that physiological forces in vivo may enable transduction via heparin sulfate proteoglycan and integrin interactions. While transduction remained the same as for unmodified vectors, the PEGylated vectors reduced innate IL-6 responses by 70 and 50% in vivo for FG-Ad and HD-Ad. These reduced innate responses paralleled similar reductions in vector uptake by macrophages in vitro and Kupffer cells in vivo. These data suggest that PEGylation of Ad vectors can reduce innate immune responses without reducing transduction in vivo. These data also suggest that nonspecific vector uptake by macrophages and Kupffer cells may be critically involved in the initial activation of innate immune responses.

Adenoviridae↗
PubMed2006

HIV-1 infection of mononuclear phagocytic cells: the case for bacterial innate immune deficiency in AIDS.

HIV-1 infection of mononuclear phagocytic cells, comprising monocytes, macrophages, and dendritic cells, has been the subject of extensive research over the past 20 years. The roles of mononuclear phagocytic cells in transmission of HIV-1 infection and as reservoirs of actively replicating virus have received particular attention. Experimental data have also accumulated about the effects of HIV-1 on the physiological function of mononuclear phagocytic cells, particularly their role in innate immunity to bacteria. The effects of HIV-1 on bacterial innate immune responses by mononuclear phagocytic cells are discussed here together with reports of direct interactions between HIV-encoded products and bacterial innate immune signalling pathways. These reports demonstrate mechanisms for HIV-mediated disruption of innate immune responses by mononuclear phagocytic cells that could provide novel therapeutic targets in HIV-infected patients. The clinical urgency is highlighted by greatly increased risk of invasive bacterial disease in this population, even in the era of highly active antiretroviral therapy. HIV-mediated injury to bacterial innate immunity provides an experimental paradigm that could broaden our overall understanding of innate immunity and be used to study responses to pathogens other than bacteria.

Acquired Immunodeficiency Syndrome↗
PubMed2006

Differential expression of ovine innate immune genes by preterm and neonatal lung epithelia infected with respiratory syncytial virus.

Preterm infants have increased susceptibility to severe manifestations of respiratory syncytial virus (RSV) infection. The cause(s) for this age-dependent vulnerability is/are not well-defined, but alterations in innate immune products have been implicated. In sheep, RSV disease severity has similar age-dependent characteristics and sheep have several related innate molecules for study during pulmonary infection including surfactant protein A (SP-A), surfactant protein D (SP-D), sheep beta defensin 1 (SBD1), monocyte chemotactic protein 1 (MCP1), and Toll-like receptor 4 (TLR4). However, the in vivo cellular gene expression as a response to RSV infection is poorly understood. In this study, the effect of RSV infection on expression of these innate immune genes was determined for bovine RSV-infected (bRSV+ fluorescence) epithelial cells, adjacent cells lacking bRSV antigen (adjoining cells lacking fluorescence), and control cells from non-infected lung using laser capture microdissection (LCM) and real-time RT-PCR. Control lambs had increased expression of innate immune molecules in full term (term) compared to preterm epithelia with statistical significance in SBD1, SP-D, and TLR4 mRNA. Infected cells (bRSV+ fluorescent cells) had consistently higher mRNA levels of SP-A (preterm and term), MCP1 (preterm and term), and SP-D (preterm). Interestingly, bRSV- cells of infected term lambs had significantly reduced SP-D mRNA expression compared to bRSV+ and control epithelia, suggesting that RSV infected cells may regulate the adjacent epithelial SP-D expression. This study defines specific innate immune components (e.g., SBD1, SP-D, and TLR4) that have differential age-dependent expression in the airway epithelia. Furthermore, cellular bRSV infection enhanced certain innate immune components while suppressing adjacent cellular SP-D expression in term animals. These in vivo gene expression results provide a framework for future studies on age-dependent susceptibility to RSV and RSV pathogenesis.

Animals↗
PubMed2001

Sepsis syndromes: understanding the role of innate and acquired immunity.

An intact innate and acquired immune response are essential for defeating systemic microbial infections. Recognition molecules, inflammatory cells, and the cytokines they produce are the principal means for host tissues to recognize invading microbes and to initiate intercellular communication between the innate and acquired immune systems. However, activation of host innate immunity may also occur in the absence of microbial recognition, through expression of internal "danger" signals produced by tissue ischemia and necrosis. When activation of the innate immune system is severe enough, the host response itself can propel the patient into a systemic inflammatory response syndrome (SIRS), or even multiple system organ failure (MSOF) and shock. Although most patients survive the initial SIRS insult, these patients remain at increased risk of developing secondary or opportunistic infections because of the frequent onset of a compensatory anti-inflammatory response syndrome (CARS). The initial activation of the innate immune response often leads to macrophage deactivation, T-cell anergy, and the rapid apoptotic loss of lymphoid tissues, which all contribute to the development of this CARS syndrome and its associated morbidity and mortality. Initial efforts to treat the septic patient with anticytokine therapies directed at the SIRS response have been disappointing, and therapeutic efforts to modify the immune response during sepsis syndromes will require a more thorough understanding of the innate and acquired immune responses and the increased apoptosis in the lymphoid tissue.

Humans↗
PubMed2006

Innate immune responses to lung-stage helminth infection induce alternatively activated alveolar macrophages.

While it is well established that infection with the rodent hookworm Nippostrongylus brasiliensis induces a strongly polarized Th2 immune response, little is known about the innate host-parasite interactions that lead to the development of this robust Th2 immunity. We exploited the transient pulmonary phase of N. brasiliensis development to study the innate immune responses induced by this helminth parasite in wild-type (WT) and severe-combined immune deficient (SCID) BALB/c mice. Histological analysis demonstrated that the cellular infiltrates caused by N. brasiliensis transit through the lungs were quickly resolved in WT mice but not in SCID mice. Microarray-based gene expression analysis demonstrated that there was a rapid induction of genes encoding molecules that participate in innate immunity and in repair/remodeling during days 2 to 4 postinfection in the lungs of WT and SCID mice. Of particular note was the rapid upregulation in both WT and SCID mice of the genes encoding YM1, FIZZ1, and Arg1, indicating a role for alternatively activated macrophages (AAMs) in pulmonary innate immunity. Immunohistochemistry revealed that nearly all alveolar macrophages became YM1-producing AAMs as early as day 2 postinfection. While the innate responses induced during the lung phase of N. brasiliensis infection were similar in complexity and magnitude in WT and SCID mice, only mice with functional T cells were capable of maintaining elevated levels of gene expression beyond the innate window of reactivity. The induction of alternatively activated alveolar macrophages could be important for dampening the level of inflammation in the lungs and contribute to the long-term decrease in pulmonary inflammation that has been associated with helminth infections.

Animals↗
PubMed2004

The infecting dose of Chlamydia muridarum modulates the innate immune response and ascending infection.

Murine vaginal infection with the obligate intracellular bacterium Chlamydia muridarum is commonly used as a model for ascending Chlamydia infections of the human female genital tract. Gamma interferon-producing Th1 cells, in concert with other mononuclear infiltrates, primarily mediate antichlamydial immunity. However, many factors modify this response, including the bacterial load. To investigate the manner in which the inoculating dose of C. muridarum modulates a genital infection, we measured innate and adaptive cell numbers, CD4+ lymphocyte cytokine profile, chemokine expression, course of infection, and pathological sequelae in genital tracts of BALB/c mice infected with doses of C. muridarum ranging from 10(4) to 10(7) inclusion-forming units. We found that the influx of both innate and adaptive immune cells responded similarly in the lower genital tract (cervical-vaginal tissues) and upper genital tract (oviduct tissues) to increasing inoculating doses. However, cells expressing the innate markers Gr-1 and CD11c were affected to a greater degree by increasing dose than lymphocytes of the adaptive immune response (Th1, CD4+, CD8+, CD19+), resulting in a change in the balance of innate and adaptive cell numbers to favor innate cells at higher infecting doses. Surprisingly, we detected greater numbers of viable chlamydiae in the oviducts at lower inoculating doses, and the number of organisms appeared to directly correlate with hydrosalpinx formation after both primary infection and repeat infection. Taken together, these data suggest that innate immune cells contribute to control of ascending infection.

Animals↗