Decreased leukocyte accumulation and delayed Bordetella pertussis clearance in IL-6^-/- mice

IL-6, a pleiotropic cytokine primarily produced by the innate immune system, has been implicated in the development of acquired immune responses, though its roles are largely undefined and may vary in the context of different diseases. Using a murine model of infection, we established that IL-6 influences the adaptive immune responses against the endemic human respiratory pathogen Bordetella pertussis. IL-6 was induced in the lungs of C57BL/6 mice by B. pertussis. IL-6^-/- mice showed a protracted infectious course and were less efficiently protected by B. pertussis vaccination than wild-type mice. Abs from IL-6^-/- mice, though lower in titer, efficiently reduced B. pertussis numbers in IL-6-sufficient mice. Pulmonary leukocyte recruitment and splenic or pulmonary T cell cytokine responses to B. pertussis, including Th1 and Th17 cytokine production, were lower in IL-6^-/- mice than in wildtype mice. Adoptive transfer of immune wild-type CD4⁺ cells ameliorated the defect of IL-6^-/- mice in the control of B. pertussis numbers. Together, these results reveal the dysregulation of multiple aspects of adaptive immune responses in B. pertussis-infected IL-6^-/- mice and suggest that IL-6 is involved in regulating Ab generation, pulmonary leukocyte accumulation, and T cell cytokine production in response to B. pertussis as well as the generation of effective vaccine-induced immunity against this pathogen.