Neutrophils Play a Protective Nonphagocytic Role in SystemicMycobacterium tuberculosisInfection of Mice

Abstract

Evidence showing that neutrophils play a protective role in the host response to infection by different intracellular parasites has been published in the past few years. We assessed this issue with regard to the infection of mice with Mycobacterium tuberculosis. We found a chronic recruitment of neutrophils to the infection foci, namely, to the peritoneal cavity after intraperitoneal infection and to the spleen and liver after intravenous inoculation of the mycobacteria. However, bacilli were never found associated with the recruited neutrophils but rather were found inside macrophages. The intravenous administration of the antineutrophil monoclonal antibody RB6-8C5 during the first week of infection led to selective and severe neutropenia associated with an enhancement of bacillary growth in the target organs of the mice infected by the intravenous route. The neutropenia-associated exacerbation of infection was most important in the liver, where a bacterial load 10-fold higher than that in nonneutropenic mice was found; the exacerbation in the liver occurred both during and after the neutropenic period. Early in infection by M. tuberculosis, neutropenic mice expressed lower levels of mRNAs for gamma interferon and inducible nitric oxide synthase in the liver compared to nondepleted mice. These results point to a protective role of neutrophils in the host defense mechanisms against M. tuberculosis, which occurs early in the infection and is not associated with the phagocytic activity of neutrophils but may be of an immunomodulatory nature.

Rapid Recruitment of Neutrophils Containing Prestored IL-12 During Microbial Infection

“…Thus, C. albicans strains that induce healing infection are capable of stimulating neutrophil IL-12 production, and this is required to control infection (3,19,29). Recent data also suggest that control of murine Mycobacterium tuberculosis infection is dependent upon an immunoregulatory function of neutrophils (30). Here, we show that depriving mice of their neutrophils at the time of infection results in decreased systemic levels of IL-12 p40 (Fig.…”

In Vivo Activity of Released Cell Wall Lipids ofMycobacterium bovisBacillus Calmette-Guérin Is Due Principally to Trehalose Mycolates

“…Neutrophil depletion during early mycobacterial infection exacerbates disease and dysregulates granuloma formation (23)(24)(25)(26). However neutrophils are associated with tissue damage and necrosis in late disease and are a feature of granulomas in gene-deletion models associated with increased susceptibility to tuberculosis (27)(28)(29)(30)(31)(32)(33).…”

Extent and distribution of linkage disequilibrium around the SLC11A1 locus

“…64 Another study demonstrated significant reduction in the expression of both receptors on neutrophils in persons with pulmonary TB and/or HIV infection. 65 Since neutrophils are known to play a protective nonphagocytic role in the initial host defense mechanisms against M. tuberculosis, 66,67 reduced expression of these receptors could impair the chemotactic response of neutrophils to IL-8 and hence the immune response in mycobacterial infection. These findings also highlight the importance of these receptors in neutrophil functions.…”