Neutrophils Dampen Adaptive Immunity in Brucellosis

Brucella organisms are intracellular stealth pathogens of animals and humans. The bacteria overcome the assault of innate immunity at early stages of an infection. Removal of polymorphonuclear neutrophils (PMNs) at the onset of adaptive immunity against Brucella abortus favored bacterial elimination in mice. This was associated with higher levels of interferon gamma (IFN-gamma) and a higher proportion of cells expressing interleukin 6 (IL-6) and inducible nitric oxide synthase (iNOS), compatible with M1 macrophages, in PMN-depleted B. abortus-infected (PMNd-Br) mice. At later times in the acute infection phase, the amounts of IFN-gamma fell while IL-6, IL-10, and IL-12 became the predominant cytokines in PMNd-Br mice. IL-4, IL-1 beta, and tumor necrosis factor alpha (TNF-alpha) remained at background levels at all times of the infection. Depletion of PMNs at the acute stages of infection promoted the premature resolution of spleen inflammation. The efficient removal of bacteria in the PMNd-Br mice was not due to an increase of antibodies, since the immunoglobulin isotype responses to Brucella antigens were dampened. Anti-Brucella antibodies abrogated the production of IL-6, IL-10, and IL-12 but did not affect the levels of IFN-gamma at later stages of infection in PMNd-Br mice. These results demonstrate that PMNs have an active role in modulating the course of B. abortus infection after the adaptive immune response has already developed.