Persistent Ehrlichia chaffeensis infection occurs in the absence of functional major histocompatibility complex class II genes.
Human monocytic ehrlichiosis is an emerging tick-borne disease caused by the rickettsia Ehrlichia chaffeensis. We investigated the impact of two genes that control macrophage and T-cell function on murine resistance to E. chaffeensis. Congenic pairs of wild-type and toll-like receptor 4 (tlr4)- or major histocompatibility complex class II (MHC-II)-deficient mice were used for these studies. Wild-type mice cleared the infection within 2 weeks, and the response included macrophage activation and the synthesis of E. chaffeensis-specific Th1-type immunoglobulin G response. The absence of a functional tlr4 gene depressed nitric oxide and interleukin 6 secretion by macrophages and resulted in short-term persistent infections for > or =30 days. In the absence of MHC-II alleles, E. chaffeensis infections persisted throughout the entire 3-month evaluation period. Together, these data suggest that macrophage activation and cell-mediated immunity, orchestrated by CD4(+) T cells, are critical for conferring resistance to E. chaffeensis.
Ganta
Roman Reddy
RR
Department of Diagnostic Medicine/Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, Kansas 66506, USA. rganta@vet.ksu.edu
Wilkerson
Melinda J
MJ
Cheng
Chuanmin
C
Rokey
Aaron M
AM
Chapes
Stephen K
SK
D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D001692:Biological Transport; D004195:Disease Models, Animal; D029721:Drosophila Proteins; D018469:Ehrlichia chaffeensis / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D016873:Ehrlichiosis / Q000235:genetics / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology; D008099:Liver / Q000276:immunology / Q000473:pathology; D017737:Macrophages, Peritoneal / Q000276:immunology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016296:Mutagenesis; D009569:Nitric Oxide / Q000096:biosynthesis; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology*; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
D000907:Antibodies, Bacterial; D029721:Drosophila Proteins; D000949:Histocompatibility Antigens Class II; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D009569:Nitric Oxide