The elimination of Anaplasma phagocytophilum requires CD4+ T cells, but is independent of Th1 cytokines and a wide spectrum of effector mechanisms.
Anaplasma phagocytophilum is a Gram-negative, obligate intracellular bacterium that exhibits a striking tropism for neutrophils. When we depleted mice of neutrophils, we found that murine susceptibility to anaplasmal infection was dependent on their presence. While serving as sites of bacterial replication, neutrophils do not seem to act as efficient killer cells in A. phagocytophilum infection, because mice deficient for antimicrobial effectors of neutrophils such as myeloperoxidase, granulocyte elastase, and cathepsin G were fully competent in pathogen elimination. To identify components of the immune system other than neutrophils that control A. phagocytophilum, we studied the course of infection in several gene-deficient mouse strains. IFN-gamma production by NK cells was important for initial defense, but not critical for pathogen elimination. In contrast, bacterial clearance was strictly dependent on CD4(+) T cells, but unexpectedly achieved in the absence of perforin, Fas/FasL and major Th1 cytokines such as IL-12, IFN-gamma, and MCP-1. These findings provide a novel paradigm for the control of an intracellular pathogen, which appears to be strikingly different from the CD4(+) T cell-, IL-12-, and IFN-gamma-dependent immunity to other intracellular bacteria.
Birkner
Katharina
K
Department of Medical Microbiology and Hygiene, Institute of Medical Microbiology and Hygiene, University of Freiburg, Freiburg, Germany.
Steiner
Birte
B
Rinkler
Christina
C
Kern
Yvonne
Y
Aichele
Peter
P
Bogdan
Christian
C
von Loewenich
Friederike D
FD
D041081:Anaplasma phagocytophilum / Q000276:immunology*; D000712:Anaplasmosis / Q000276:immunology; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D019013:CD40 Antigens / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D051379:Mice; D009504:Neutrophils / Q000276:immunology; D013154:Spleen / Q000276:immunology; D013997:Time Factors
D019013:CD40 Antigens; D016207:Cytokines; D000949:Histocompatibility Antigens Class II