Early granuloma formation after aerosol Mycobacterium tuberculosis infection is regulated by neutrophils via CXCR3-signaling chemokines.
Among the first cells to invade a site of infection, polymorphonuclear neutrophils (PMN) play an important role in the control of numerous infections. While PMN are considered critical for control of acute infections, their role in chronic infections remains less well understood. Here we report that PMN are essential for accurate early granuloma formation during chronic M. tuberculosis infection without influencing mycobacterial growth restriction. The PMN-mediated regulation of granuloma formation depended on chemokines signaling through CXCR3, in particular MIG, as indicated by immune histochemical analysis of lung sections from C57BL/6 wild-type and CXCR3(-/-) mutant mice and supported by microarray transcriptome analysis. Hence, PMN play a central role in regulating the focal granulomatous response in the lung, and this early granuloma formation can be segregated from long-term protection against pulmonary M. tuberculosis infection.
D000336:Aerosols; D000818:Animals; D054370:Chemokine CXCL9; D019743:Chemokines, CXC / Q000096:biosynthesis; D006099:Granuloma / Q000209:etiology*; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis; D008168:Lung / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000502:physiology; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D013601:T-Lymphocytes / Q000502:physiology; D014376:Tuberculosis / Q000276:immunology*
D000336:Aerosols; C080810:CXCL9 protein, human; C515187:CXCR3 protein, human; D054370:Chemokine CXCL9; D019743:Chemokines, CXC; C515188:Cxcr3 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D016692:Receptors, Antigen, T-Cell, gamma-delta; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine