Crucial Role of Gamma Interferon-Producing CD4+Th1 Cells but Dispensable Function of CD8+T Cell, B Cell, Th2, and Th17 Responses in the Control of Brucella melitensis Infection in Mice

Abstract

ABSTRACTBrucellaspp. are facultative intracellular bacterial pathogens responsible for brucellosis, a worldwide zoonosis that causes abortion in domestic animals and chronic febrile disease associated with serious complications in humans. There is currently no approved vaccine against human brucellosis, and antibiotic therapy is long and costly. Development of a safe protective vaccine requires a better understanding of the roles played by components of adaptive immunity in the control ofBrucellainfection. The importance of lymphocyte subsets in the control ofBrucellagrowth has been investigated separately by various research groups and remains unclear or controversial. Here, we used a large panel of genetically deficient mice to compare the importance of B cells, transporter associated with antigen processing (TAP-1), and major histocompatibility complex class II-dependent pathways of antigen presentation as well as T helper 1 (Th1), Th2, and Th17-mediated responses on the immune control ofBrucella melitensis16 M infection. We clearly confirmed the key function played by gamma interferon (IFN-γ)-producing Th1 CD4+T cells in the control ofB. melitensisinfection, whereas IFN-γ-producing CD8+T cells or B cell-mediated humoral immunity plays only a modest role in the clearance of bacteria during primary infection. In the presence of a Th1 response, Th2 or Th17 responses do not really develop or play a positive or negative role during the course ofB. melitensisinfection. On the whole, these results could improve our ability to develop protective vaccines or therapeutic treatments against brucellosis.