Neutrophil-macrophage cooperation in the host defence against mycobacterial infections.

CD-1 mice inoculated intraperitoneally with Mycobacterium avium, M. bovis, M. microti or M. kansasii showed a persistent peritoneal granulocytosis (above 10(6) cells, i.e. more than 15% of total cells) throughout the 3 month period of infection studied. By contrast, in mice inoculated with the non-pathogenic M. aurum or with heat-killed M. avium the number of granulocytes decreased progressively after the first 15 days. No mycobacteria were found in granulocytes except in the first 2 days of infection. The mycobacteria-induced chronic granulocytosis was accompanied by phagocytosis of granulocytes by macrophages. Throughout the 3 months of infection, macrophages were found to contain intracellular lactoferrin. Macrophages with lactoferrin were also found in subcutaneous infection caused by M. marinum and in systemic infection caused by M. avium or M. kansasii. The in vitro activity of mouse peritoneal macrophages against M. avium and M. microti was increased after ingestion of granulocyte material by macrophages. These results lead us to propose that granulocytes participate in the host response to mycobacterial infections, not as phagocytes but rather through an indirect mechanism, as a source for the macrophages of molecules involved in antimicrobial mechanisms (e.g., lactoferrin and myeloperoxidase) lacking in the mature macrophage.