Neutrophils play a protective nonphagocytic role in systemic Mycobacteriumtuberculosis infection of mice

Evidence showing that neutrophils play a protective role in the host respon se 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 neu trophils to the infection foci, namely, to the peritoneal cavity after intr aperitoneal infection and to the spleen and liver after intravenous inocula tion of the mycobacteria. However, bacilli were never found associated with the recruited neutrophils but rather were found inside macrophages, The in travenous 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 exac erbation of infection was most important in the liver, where a bacterial lo ad 10-fold higher than that in nonneutropenic mice was found; the exacerbat ion in the liver occurred both during and after the neutropenic period. Ear ly in infection by M, tuberculosis, neutropenic mice expressed lower levels of mRNAs for gamma interferon and inducible nitric oxide synthase in the l iver compared to nondepleted mice. These results point to a protective role of neutrophils in the host defense mechanisms against M, tuberculosis, whi ch occurs early in the infection and is not associated with the phagocytic activity of neutrophils but may be of an immunomodulatory nature.