Phagocytosis of apoptotic cells increases the susceptibility of macrophages to infection with Coxiella burnetii phase II through down-modulation of nitric oxide production.
Coxiella burnetii, the agent of Q fever in humans and coxiellosis in other mammals, is an obligate intracellular bacterium which is sheltered and multiplies within typically large phagolysosome-like replicative vacuoles (LRVs). We have previously shown that, compared with fibroblasts, mouse resident peritoneal macrophages control the development of LRVs and bacterial multiplication within these vacuoles. Earlier experiments with the nitric oxide (NO) synthase inhibitor aminoguanidine (AG) revealed that the control is exerted by NO induced by the bacteria. We report here that phagocytosis of apoptotic-like, but not of aldehyde-killed, lymphocytes by the macrophages reduced the production of NO induced by the bacteria and increased the development of LRVs and, therefore, the total bacterial load in the cultures. Experiments with macrophages from mice deficient for inducible NO synthase (iNOS(-)/(-)) confirmed the involvement of NO in the control of infection, since neither apoptotic lymphocytes nor AG affected the development of LRVs in these phagocytes. Since macrophages are important for the clearance of apoptotic bodies and C. burnetii is able to induce apoptosis in human monocytes, the phenomenon shown here may be biologically relevant to the development of Q fever and coxiellosis.
Zamboni
Dario S
DS
Departamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, SP 04023-062 Brazil. dario.zamboni@yale.edu
Rabinovitch
Michel
M
D000818:Animals; D017209:Apoptosis; D002478:Cells, Cultured; D016997:Coxiella burnetii / Q000472:pathogenicity* / Q000648:ultrastructure; D004198:Disease Susceptibility; D015536:Down-Regulation; D006801:Humans; D008264:Macrophages / Q000276:immunology / Q000382:microbiology* / Q000502:physiology; D051379:Mice; D018613:Microscopy, Confocal; D009569:Nitric Oxide / Q000096:biosynthesis*; D010587:Phagocytosis; D010588:Phagosomes / Q000382:microbiology; D011778:Q Fever / Q000382:microbiology; D014617:Vacuoles / Q000382:microbiology
D009569:Nitric Oxide