Avian immunology: from fundamental immune mechanisms to the integrative management of poultry.
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Animal Husbandry↗
Biomedical subjects
R R Dietert
Publications and source records attributed to R R Dietert.
Profiles of chicken macrophage effector functions.
In contrast to the mammalian system, avian species lack the so-called "resident" or "harvestable" macrophage population in the abdominal exudate. However, macrophages can be recruited into the chicken's abdominal cavity (presumably from the blood monocyte pool) if an inflammatory agent such as Sephadex is injected. The kinetics of inflammatory cell recruitment in terms of time, cell type, and state of activation to perform a particular effector function is currently an active area of research. This report will provide information on several chicken macrophage effector functions, including in vivo chemotaxis, phagocytosis, bacterial uptake and killing, biosynthesis of nitric oxide and various enzymes, and monokines such as interleukin-1 and granulocyte colony-stimulating factor.
Acid Phosphatase↗
Environment-immune interactions.
The need for effective immune function for the maintenance of health has been clearly established in both agriculturally significant animal species and humans. Intensive agricultural practices present production species with numerous disease challenges during the rearing period. Environmental factors represent a ubiquitous, yet frequently manageable, category of immunomodulators that can influence immune performance and ultimately disease susceptibility or resistance. However, strategies for assessing overall immune potential have not been widely implemented for agricultural species. This is in contrast to the use of immune evaluation for human health considerations. Immune assessment relative to environmental-immune interactions can produce benefits in two areas. First, the efficiency of the production operation can be enhanced. Second, the welfare of the animals during the production cycle can be optimized. This paper presents an overview of environmental factors known to influence the immune function of poultry and the opportunities to manage environmental factors to benefit the health of the animals. In addition, the paper discusses the status of immunological assessment for humans and laboratory animals and proposes potential immune assessment panels that could serve as a tool to optimize the environmental management of poultry populations.
Animal Husbandry↗
Avian macrophages: contribution to cellular microenvironment and changes in effector functions following activation.
The capacity of macrophages to generate metabolites and monokines having effector and regulatory functions can result in a major impact on their cellular microenvironment. Macrophage products synthesized in response to bacterial lipopolysaccharide stimulation include reactive oxygen and nitrogen intermediates as well as tumor necrosis factor (TNF). These secreted products of macrophages exhibit bioactivity either locally or systemically. Although the mechanism of action of avian monokines such as TNF-like factor may be similar to their mammalian counterparts, chicken TNF seems to lyse cells of chicken origin and not of mammalian origin. Furthermore, the generation and activity of products such as TNF is directly influenced by environmental stressors such as heat and toxins.
Animals↗
Direct measurement of nitric oxide in headspace gas produced by a chicken macrophage cell line in a closed culture system.
A simple and rapid method was applied for direct measurement of nitric oxide (NO) gas produced by cultured macrophages using a modified chemiluminescence detector, the thermal energy analyzer (TEA). HD11 chicken macrophages (1-3 x 10(6)/ml) were cultured on microcarrier beads (100 mg/ml) in 140 ml air-tight glass jars (5 ml cell suspension per jar) containing 0.5 micrograms/ml of LPS and different concentrations of L-arginine. Headspace gas was sampled at 24 hours of culture via a rubber septum and directly injected into a TEA with a liquid nitrogen trap set at -130 to -140 degrees C. The concentration of NO in the gas sample was quantified using a standard gas mixture of NO (2 microliters/L) in nitrogen. Gas samples from L-arginine-supplemented cultures contained NO (0.028-0.066 pl/microliter), whereas NO was not detected in samples from controls. These results suggest that chicken macrophages synthesize NO gas in a dose-dependent manner relative to L-arginine concentration.
Animals↗
Macrophage antimicrobial functions in a chicken MHC chromosome dosage model.
Macrophages respond to certain inflammatory signals with a marked increase in respiratory burst and the production of reactive oxygen intermediates; these metabolites play an essential role in the destruction of invading microorganisms. In this study, macrophage antibacterial inflammatory responses were compared among chickens having two (disomic), three (trisomic), or four (tetrasomic) copies of the major histocompatibility complex (MHC)-encoding microchromosome (B15 haplotype). Phorbol myristate acetate (PMA)-stimulated superoxide anion (O2-) production by cross-linked dextran (Sephadex)-elicited peritoneal macrophages was measured at early (4 h), intermediate (24 h), and late (42 h) stages of the inflammatory response using ferrocytochrome c reduction. Significantly elevated O2- production was observed for trisomic versus disomic macrophages during both early and intermediate stages of the inflammatory response. Late in the response, tetrasomic macrophages produced a significantly higher level of O2- than disomic cells. When PMA was used to trigger hydrogen peroxide (H2O2) production, no significant genotype difference was found for any stage of the inflammatory response. Phagocytosis of heat-killed Salmonella enteritidis by macrophages differed among the three genotypes: trisomic macrophages were superior to disomic cells during early inflammation, no genotypic difference was observed at the intermediate stage, and disomic cells had greater phagocytic capacity than aneuploid macrophages late in the response. Likewise, when S. enteritidis was cultured with macrophages to induce oxygen intermediate secretion, H2O2 production followed a kinetic pattern among the genotypes similar to that observed for bacterial phagocytosis. Endogenous superoxide dismutase (SOD), catalase, and glutathione peroxidase (GP) activities were determined for the macrophages during intermediate and late inflammatory stages. Tetrasomic macrophages had reduced SOD activity at the late stage, no significant difference was observed in catalase activity among genotypes at either time point, and trisomic macrophages had enhanced GP activity compared to disomic cells at both time points. These results indicate that differences in MHC gene dosage are associated with differences in chicken macrophage activation for the acquisition of selected antibacterial functions.
Aneuploidy↗
Distribution and inducibility of a P450I activity in cellular components of the avian immune system.
The level of expression of the cytochrome P450 system in an immune tissue could influence the sensitivity of that immune tissue to damage by xenobiotics. The capacity of immune organs and their cellular components for P450I-catalyzed metabolism was assayed in the 4-week-old chicken using the P450I-specific ethoxyresorufin-O-deethylase (EROD) assay and the P450I-inducer, 3,4,3',4'-tetrachlorobiphenyl (TCB). After induction by TCB, EROD was detectable in microsomes from whole thymus, bursa and in peritoneal exudate cells (containing primarily macrophages) at levels of 28.3, 7.2 and 1.3 pmol/mg microsomal protein/min, respectively; the level in control liver was 89.9 pmol/mg microsomal protein/min. No activity was detected in these immune tissues without induction. The P450I specific in vitro inhibitor, alpha-naphthoflavone (NF) inhibited the TCB-induced liver and immune tissue EROD by 50% at concentrations in the range of 0.07-0.1 microM. The cellular distribution of EROD in the bursa and thymus was studied in lymphocytes and supporting tissue cells after their separation by density gradient centrifugation. Much higher TCB-induced EROD was detected in immune tissue supporting cells than in lymphocytes, particularly in the thymus. The P450I in the supporting tissue of the bursa and thymus at 1 week post-hatch was also measured after eradication of the lymphocytes in both immune tissues by in ovo administration of CP. TCB-induced EROD was 12-fold higher in the lymphocyte-depleted thymus than in normal thymus, with a less marked but similar pattern in the bursa.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Assessment of neonatal avian inflammatory macrophage function following embryonic cyclophosphamide exposure.
Inflammatory macrophage recruitment and function were examined in 4-5-week-old chickens which had received two doses of cyclophosphamide (CP) or vehicle (dH2O) during late embryogenesis (18 and 19 days of incubation). Mononuclear leukocyte chemotaxis to N-formyl-methionyl-leucyl-phenylalanine (FMLP) and hematological parameters were unchanged in CP-treated vs control chickens. Peritoneal exudate cells (PECs) elicited in response to intraperitoneal (i.p.). Sephadex injection did not differ in CP-treated vs control chickens with respect to cell number, cell type, superoxide anion production, or cell surface expression of Ia and transferrin receptor (TfR) antigens. The CP-treated chickens did exhibit the expected decrease in bursa weight; male chickens exposed to CP also had inhibited testes growth. Although embryonic exposure to CP at this dose results in irreversible bursal damage and subsequent impaired humoral immunity, it appears that there are no long-lasting effects on avian inflammatory macrophage function.
Animals↗
Dietary arginine influences Rous sarcoma growth in a major histocompatibility B complex progressor genotype.
L-Arginine (L-Arg) can serve as a substrate for the production of reactive nitrogen intermediates. One of these metabolites, nitric oxide, has been shown to possess significant antitumor properties in vitro. To investigate the importance of this system in vivo, we have examined the dietary L-Arg host tumor interaction in the chicken. Since chickens are incapable of de novo L-Arg synthesis, concentration of this amino acid is readily controlled by diet. Line UNH 105 New Hampshire chickens having the major histocompatibility complex genotype, B24/B24, were used to study in vivo effects of dietary L-Arg on Rous sarcoma growth. After 5 weeks on a standard diet, 119 chicks were fed either a basal (0.92% L-Arg) diet or a high arginine (2.40% L-Arg) diet. One week later, chicks were wing-web inoculated with subgroup A Rous sarcoma virus. Tumor growth was monitored weekly for 12 weeks after inoculation. Plasma L-Arg levels and body weights from birds on each dietary treatment were analyzed. Neither body weight gains nor latent period for tumor development was affected by diet. However, plasma L-Arg levels were significantly different between dietary treatments (basal, 0.245 +/- 0.01 mumol/ml; high, 0.738 +/- 0.03 mumol/ml). In addition, mean tumor size scores were significantly (P less than 0.05) lower over time in chickens fed the high L-Arg diet. The results suggest that dietary L-Arg in excess of the amount required for growth reduces tumor load.
Animals↗
L-arginine-dependent production of a reactive nitrogen intermediate by macrophages of a uricotelic species.
L-arginine-dependent production of reactive nitrogen intermediates (RNIs: nitric oxide, nitrite, and nitrate) by mammalian macrophages has been proposed to occur via an L-arginine oxidative deimination pathway and is known to be responsible for certain antineoplastic and antimicrobial effector functions. The present study represents the first examination of this pathway in a non-mammalian vertebrate. Because chickens, unlike mammals, lack a urea cycle and are incapable of de novo synthesis of L-arginine, the possible existence of an avian macrophage pathway for production of RNIs is questionable. We have defined conditions under which chicken macrophages are able to produce nitrite. Sephadex-elicited chicken peritoneal macrophages required a bacterial lipopolysaccharide (LPS from Escherichia coli) signal to produce nitrite during 24 hour cultures in the presence of L-arginine. As little as 5 ng/ml LPS resulted in significant nitrite production in culture. The relationship of nitrite production to both LPS and L-arginine levels was dose-dependent. D-arginine was unable to substitute for L-arginine but also produced no inhibitory effect. In contrast, L-NG-monomethyl arginine showed a significant inhibitory effect on nitrite production. A virus-transformed chicken macrophage cell line, HD11, also produced nitrite in a dose-dependent manner relative to both LPS and L-arginine concentration. Concentrations as low as 5 ng/ml LPS and 0.1 mM L-arginine resulted in significant nitrite production, while maximum levels of nitrite production were obtained using greater than or equal to 0.5 micrograms/ml LPS and greater than or equal to 0.4 mM L-arginine. These results indicate that chicken macrophages can produce RNIs. This production is dependent upon activation and is influenced by local L-arginine concentration. Moreover, because the chicken does not possess the ability to synthesize arginine and has an absolute nutritional requirement for this amino acid, the chicken represents a highly controllable system to examine the in vivo effects of L-arginine on macrophage-related immune functions.
Animals↗
Genetic control of cell-mediated immunity in chickens.
The present review briefly outlines the effector cells and molecules influencing cell-mediated immunity. Emphasis is placed on the genes determining these molecules in mammals and in the chicken, including genes for cytokines and cytokine receptors. The review concludes with a tabular presentation containing examples of specific genetic influences on cell-mediated immunity in chickens and mammals.
Animals↗
Avian inflammatory macrophage function: shifts in arachidonic acid metabolism, respiratory burst, and cell-surface phenotype during the response to Sephadex.
The avian inflammatory response to intraperitoneal (i.p.) Sephadex injection produces macrophages which display characteristics of an increasingly activated state over time. We examined elicited chicken peritoneal exudate cells (PECs) with respect to superoxide anion production, arachidonic acid metabolism and cell surface Ia and transferrin receptor (TfR) expression from 4 to 96 h after i.p. stimulation. Avian PECs showed the highest level of superoxide release when harvested just 4 h after injection, and did not produce PGE2 or 6-keto PGF1 alpha. Early (4-h) PECs produced elevated amounts of thromboxane as compared to later (42-h) macrophages. Expression of both Ia and TfR increased between 4 and 24 h after Sephadex stimulation; TfR remained elevated through 96 h, but Ia declined after 42 h. Some aspects of chicken macrophage regulation of superoxide anion, thromboxane release, and surface antigen expression are in contrast with those reported for mouse macrophages.
Animals↗
Dynamics of avian inflammatory response to cross-linked dextran. Changes in avian blood leukocyte populations.
A model inflammatory compound, cross-linked dextran (Sephadex), which preferentially recruits macrophages, was used to examine shifts in chicken leukocyte distribution and monocyte functional status during the inflammatory response. Following intraperitoneal Sephadex administration, total leukocyte counts were transiently elevated because of a fivefold increase in circulating heterophils (granulocytes). While both heterophils and monocytes may become demarginated, primarily monocytes enter the peritoneal cavity in response to Sephadex. Since leukocyte chemotaxis is an important feature of the inflammatory response, this parameter was analyzed during the recruitment period. The optimum conditions for in vitro chicken mononuclear leukocyte chemotaxis to N-formyl-methionyl-leucyl-phenyl-alanine (FMLP) were defined and compared with those for the chicken macrophage-like cell line, HD11. Mononuclear leukocytes from birds injected 6 or 12 h previously with Sephadex were significantly decreased in chemotactic ability when compared with controls; at 24 h after injection, the response to FMLP had returned to normal. This system offers an opportunity to examine differential effects of inflammatory stimuli upon leukocyte function and distribution.
Animals↗
B-congenic chickens differ in macrophage inflammatory responses.
The influence of the chicken major histocompatibility (B) complex (MHC) on monocyte and macrophage recruitment and activation was examined using fully developed 15I5-B congenic White Leghorn lines (ten backcross generations). The phagocytic activity of Sephadex-elicited peritoneal macrophages for sheep red blood cells (SRBCs) was highest in lines 15.7-B2 and 15.P-B13 and lowest in 15.15I-B5 and 15.N-B21. The same pattern of phagocytic activity was obtained when LPS (E. coli) was used as the in vivo elicitor-activator of peritoneal macrophages. Lines with B2 and B13 haplotypes had elevated percentages of phagocytic macrophages and a higher internalization activity per cell than did B5 and B21 congenic chickens. Differential peritoneal macrophage function between congenic lines was further supported by quantitation of superoxide anion release. B2 and B13 haplotypes were associated with high activity in contrast with B5, which was low, and 15I5 (B15) and B21 which were intermediate for superoxide anion release by macrophages. In vitro activation of blood monocytes with LPS resulted in similar line differences for SRBC phagocytic activity as were observed with in vivo Sephadex and LPS activation. In contrast, chemotaxis of blood mononuclear leukocytes to f-met-leu-phe produced a reciprocal response pattern among the haplotypes. Cells from lines with haplotypes B5 and B21 were superior to those of B2, B13, and B15 congenic lines in their directed migration towards this chemoattractant. All functional differences occurred despite similarities among lines in the cellular profiles of both elicited peritoneal exudate cells and isolated blood mononuclear cells.
Animals↗
Induction of hepatic metallothionein by intraperitoneal metal injection: an associated inflammatory response.
The nature of hepatic metallothionein (MT) induction by several metals and its relationship to an inflammatory response was studied in chicks. Intraperitoneal (ip) injection of chromium (Cr), managanese, and iron (Fe) caused a much greater increase in hepatic MT (10.2-, 9.0-, and 6.8-fold) compared with cobalt and nickel (2.5- and 2.9-fold); thus not all transition metals are effective. Cr3+ caused markedly greater hepatic MT accumulation than Cr6+, suggesting that the ionic nature of the metal is an important factor. Small organic complexes of Fe (ferrous gluconate or lactate, 6.2-fold) caused significantly greater accumulation of hepatic MT than ferric dextran (1.4-fold), a large organic aggregate. In vitro data from chick hepatocytes and/or fibroblasts clearly indicated that Fe does not effect the induction of MT directly. The role of inflammation, as measured by recruitment of peritoneal exudate cells (PEC), was examined. Endotoxin (LPS), Sephadex (S), and Fe elicited significant elevations in PEC number at 24 h posttreatment (S), and Fe elicited significant elevations in PEC number at 24 h posttreatment (S = Fe greater than LPS much greater than control). The percentage of heterophils but not macrophages was significantly correlated with the accumulation and induction of hepatic MT. In a similar experiment with Cr, we demonstrated that Cr3+ but not Cr6+ stimulated MT messenger RNA accumulation and concomitant hetereophil infiltration at 3 h after injection. Our results indicate that the induction of hepatic MT by the parenteral administration of a number of metals is dependent on the chemical nature of the metal and is associated with an inflammatory response.
Animals↗
3-Methylcholanthrene-induced immunosuppression in mice to Trichinella spiralis antigens.
The immunosuppressive effects of in vivo (subcutaneous) exposure to 40 or 80 mg/kg 3-methylcholanthrene (MC) were examined in aryl hydrocarbon hydroxylase (AHH) responsive C57BL/6 (B6) and AHH non-responsive DBA/2 (D2) inbred strains of mice. Twenty-four hours after treatment with carcinogen or vehicle alone, animals were primed with crude L1 muscle larvae antigen from T. spiralis. Immune status was assessed in vitro after six days as antigen-specific lymphoproliferation. The proliferation of splenocytes from MC-treated D2 and B6 mice was significantly impaired compared to controls. To examine the cellular basis of the immunosuppression, primed splenocytes from control and MC-treated mice were separated into adherent and non-adherent fractions on Sephadex G-10 columns. When antigen-pulsed adherent cells from MC-treated B6 and D2 mice were recombined with control non-adherent cells from syngeneic and B6D2F1 mice, T-cell proliferation was significantly reduced. This suppression was not observed with the addition of increased numbers of adherent cells. Non-adherent cells from MC-treated mice showed a decreased capacity to respond to the presence of control antigen-pulsed adherent cells from appropriate mice. These results suggest that MC treatment has a similar suppressive effect on the immune responses of both B6 and D2 mice that involves the quality of accessory cell-T-cell interactions.
Animals↗
Toxic effects of methyl methanesulfonate (MMS) on activated macrophages from chickens.
Adherent peritoneal exudate cells rich in macrophages were harvested from Cornell K-strain chickens 42 hr after i.p. stimulation with Sephadex G-50. Glass-adherent monolayers were obtained on coverslips and subjected to in vitro exposure to methyl methanesulfonate (MMS) at various doses for 1 hr. Solvent (0.17% ethanol final concentration) and sham (RPMI 1640 growth media) exposures were also performed. At selected times after exposure, the macrophages were analyzed for cell viability, adherence, DNA damage, and functional activity. Although MMS doses of 5 x 10(-3) M and 1 x 10(-3) M concentrations resulted in significant cytoxicity, 2 x 10(-4) M had no significant cytotoxic effect. However, this exposure resulted in DNA damage as measured by alkaline elution. Concomitant with the DNA damage was a significant decrease in the phagocytic activity of macrophages. Repair of MMS-induced DNA lesions in macrophages was indicated by a normal DNA alkaline elution profile 10 hr postrecovery. Functional activity of cells also returned to normal levels. In contrast, the incidence of Fc receptor-positive cells detected by rosetting increased immediately after MMS exposure, and phagocytosis of opsonized SRBCs was not affected by 2 x 10(-4) M MMS treatment. Similarly, MMS treatment did not alter the acid phosphatase activity of macrophages. However, bactericidal ability of MMS-treated macrophages for unopsonized Escherichia coli was significantly depressed. These results suggest that the avian macrophage is a useful target cell for examining possible relationships between genotoxic and immunotoxic effects of environmental mutagens.
Animals↗
The relative importance of Ah versus H-2 genotype on Trichinella resistance following exposure to 3-methylcholanthrene.
The relative influence of Ah vs H-2 genotype on the outcome of Trichinella spiralis (Tsp) infections of mice was examined following methylcholanthrene (MC) treatment. Female mice of four inbred strains were treated with MC and infected 24 h later with Tsp muscle larvae. The strains, with their respective major histocompatibility complex (MHC) haplotype, aryl hydrocarbon hydroxylase responsiveness (Ah phenotype) and level of susceptibility to Tsp infection, were: C3HeB/FeJ (C3), H-2k, Ahb, Tsp susceptible; C57BL/10.BR (B10.BR), H-2k, Ahb, Tsp susceptible; C57BL/10.Q (B10.Q), H-2q, Ahb, Tsp resistant; and AKR/J (AK), H-2k, Ahd, Tsp resistant. The proliferative response of splenic lymphocytes to crude Tsp L1 stage antigen was significantly depressed in all MC-treated groups, with the exception of the B10.BR strain. MC administered at 40 mg/kg impaired the ability of C3 and B10.Q mice to eliminate adult worms. At 80 mg/kg, C3 strain mice were also impaired, as well as AK strain mice. The fecundity of female worms recovered from B10 or AK strain mice was not significantly altered by MC treatment, although female worms from treated C3 mice exhibited increased fecundity on day 9 post infection. Muscle larvae burdens of MC-treated B10 and C3 mice were elevated, while those of AK strain mice were unaffected. These data suggest that with acute exposures to MC, the immunogenetic resistance or susceptibility of a given mouse strain may have a more pronounced effect on immune depression and the severity of Tsp infection than does the Ah phenotype.
Animals↗