Biomedical subjects
Abdellatif Tazi
Publications and source records attributed to Abdellatif Tazi.
DC-SIGN induction in alveolar macrophages defines privileged target host cells for mycobacteria in patients with tuberculosis.
BACKGROUND: Interplays between Mycobacterium tuberculosis, the etiological agent of tuberculosis (TB) in human and host professional phagocytes, namely macrophages (Mphis) and dendritic cells (DCs), are central to immune protection against TB and to TB pathogenesis. We and others have recently shown that the C-type lectin dendritic cell-specific intercellular adhesion molecule-3 grabbing nonintegrin (DC-SIGN; CD209) mediates important interactions between mycobacteria and human monocyte-derived DCs (MoDCs) in vitro. METHODS AND FINDINGS: In order to explore the possible role of DC-SIGN in M. tuberculosis infection in vivo, we have analysed DC-SIGN expression in broncho-alveolar lavage (BAL) cells from patients with TB (n = 40) or with other non-mycobacterial lung pathologies, namely asthma (n = 14) and sarcoidosis (n = 11), as well as from control individuals (n = 9). We show that in patients with TB, up to 70% of alveolar Mphis express DC-SIGN. By contrast, the lectin is barely detected in alveolar Mphis from all other individuals. Flow cytometry, RT-PCR, and enzyme-linked immunosorbent assay analyses of BAL-derived fluids and cells indicated that M. tuberculosis infection induces DC-SIGN expression in alveolar Mphis by a mechanism that is independent of Toll-like receptor-4, interleukin (IL)-4, and IL-13. This mechanism most likely relies on the secretion of soluble host and/or mycobacterial factors that have yet to be identified, as both infected and uninfected bystander Mphis were found to express DC-SIGN in the presence of M. tuberculosis. Immunohistochemical examination of lung biopsy samples from patients with TB showed that the bacilli concentrate in pulmonary regions enriched in DC-SIGN-expressing alveolar Mphis in vivo. Ex vivo binding and inhibition of binding experiments further revealed that DC-SIGN-expressing alveolar Mphis constitute preferential target cells for M. tuberculosis, as compared to their DC-SIGN- counterparts. In contrast with what has been reported previously in MoDCs in vitro, ex vivo DC-SIGN ligation by mycobacterial products failed to induce IL-10 secretion by alveolar Mphis, and IL-10 was not detected in BALs from patients with TB. CONCLUSION: Altogether, our results provide further evidence for an important role of DC-SIGN during TB in humans. DC-SIGN induction in alveolar Mphis may have important consequences on lung colonization by the tubercle bacillus, and on pulmonary inflammatory and immune responses in the infected host.
[Update on sarcoidosis].
Since the first description more than a century ago, intensive research continues to focus on sarcoidosis. Based on our current knowledge, sarcoidosis can be considered as an immune syndrome resulting from a variable combination of predisposing genetic, ethnic, and environmental factors. Over the last few years, several teams have proposed a link between certain genetic polymorphisms, particularly of the HLA system, and the risk of development or progression of sarcoidosis. Other pathogenic mechanisms involved in the formation of the sarcoid granuloma are becoming more clear and have led to the development of new therapeutic approaches such as anti-TNF currently being evaluated in multicentric trials.
The prognosis of acute respiratory failure in critically ill cancer patients.
Acute respiratory failure (ARF) in patients with cancer is frequently a fatal event. To identify factors associated with survival of cancer patients admitted to an intensive care unit (ICU) for ARF, we conducted a prospective 5-year observational study in a medical ICU in a teaching hospital in Paris, France. The patients were 203 cancer patients with ARF mainly due to infectious pneumonia (58%), but also noninfectious pneumonia (9%), congestive heart failure (12%), and no identifiable cause (21%). We measured clinical characteristics and ICU and hospital mortality rates.ICU mortality was 44.8% and hospital mortality was 47.8%. Noninvasive mechanical ventilation was used in 79 (39%) patients and conventional mechanical ventilation in 114 (56%), the mortality rates being 48.1% and 75.4%, respectively. Among the 14 patients with late noninvasive mechanical ventilation failure (>48 hours), only 1 survived. The mortality rate was 100% in the 19 noncardiac patients in whom conventional mechanical ventilation was started after 72 hours. By multivariable analysis, factors associated with increased mortality were documented invasive aspergillosis (odds ratio [OR], 2.13; 95% confidence intervals [CI], 1.05-14.74), no definite diagnosis (OR, 3.85; 95% CI, 1.26-11.70), vasopressors (OR, 3.19; 95% CI, 1.28-7.95), first-line conventional mechanical ventilation (OR, 8.75; 95% CI, 2.35-35.24), conventional mechanical ventilation after noninvasive mechanical ventilation failure (OR, 17.46; 95% CI, 5.04-60.52), and late noninvasive mechanical ventilation failure (OR, 10.64; 95% CI, 1.05-107.83). Hospital mortality was lower in patients with cardiac pulmonary edema (OR, 0.16; 95% CI, 0.03-0.72). Survival gains achieved in critically ill cancer patients in recent years extend to patients requiring ventilatory assistance. The impact of conventional mechanical ventilation on survival depends on the time from ICU admission to conventional mechanical ventilation and on the patient's response to noninvasive mechanical ventilation.