title: Murine and bovine γδ T cells enhance innate immunity against Brucella abortus infections.
abstract: γδ T cells have been postulated to act as a first line of defense against infectious agents, particularly intracellular pathogens, representing an important link between the innate and adaptive immune responses. Human γδ T cells expand in the blood of brucellosis patients and are active against Brucella in vitro. However, the role of γδ T cells in vivo during experimental brucellosis has not been studied. Here we report TCRδ(-/-) mice are more susceptible to B. abortus infection than C57BL/6 mice at one week post-infection as measured by splenic colonization and splenomegaly. An increase in TCRγδ cells was observed in the spleens of B. abortus-infected C57BL/6 mice, which peaked at two weeks post-infection and occurred concomitantly with diminished brucellae. γδ T cells were the major source of IL-17 following infection and also produced IFN-γ. Depletion of γδ T cells from C57BL/6, IL-17Rα(-/-), and GMCSF(-/-) mice enhanced susceptibility to B. abortus infection although this susceptibility was unaltered in the mutant mice; however, when γδ T cells were depleted from IFN-γ(-/-) mice, enhanced susceptibility was observed. Neutralization of γδ T cells in the absence of TNF-α did not further impair immunity. In the absence of TNF-α or γδ T cells, B. abortus-infected mice showed enhanced IFN-γ, suggesting that they augmented production to compensate for the loss of γδ T cells and/or TNF-α. While the protective role of γδ T cells was TNF-α-dependent, γδ T cells were not the major source of TNF-α and activation of γδ T cells following B. abortus infection was TNF-α-independent. Additionally, bovine TCRγδ cells were found to respond rapidly to B. abortus infection upon co-culture with autologous macrophages and could impair the intramacrophage replication of B. abortus via IFN-γ. Collectively, these results demonstrate γδ T cells are important for early protection to B. abortus infections.
authors.affiliation: Department of Immunology and Infectious Diseases, Montana State University, Bozeman, Montana, United States of America.
authors.forename: Jerod A
authors.initials: JA
authors.lastname: Skyberg
authors.forename: Theresa
authors.initials: T
authors.lastname: Thornburg
authors.forename: Maryclare
authors.initials: M
authors.lastname: Rollins
authors.forename: Eduardo
authors.initials: E
authors.lastname: Huarte
authors.forename: Mark A
authors.initials: MA
authors.lastname: Jutila
authors.forename: David W
authors.initials: DW
authors.lastname: Pascual
mesh_terms: D000818:Animals; D002003:Brucella abortus / Q000254:growth & development / Q000276:immunology*; D002006:Brucellosis / Q000276:immunology* / Q000517:prevention & control; D002007:Brucellosis, Bovine / Q000276:immunology* / Q000517:prevention & control; D002417:Cattle; D049109:Cell Proliferation; D020869:Gene Expression Profiling; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D020381:Interleukin-17 / Q000096:biosynthesis; D016131:Lymphocyte Subsets / Q000276:immunology; D008264:Macrophages / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000172:deficiency / Q000276:immunology*; D013154:Spleen / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D020381:Interleukin-17; D016692:Receptors, Antigen, T-Cell, gamma-delta; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor