Abstract
We have previously demonstrated that B cells can shape the immune response to Mycobacterium tuberculosis, including the level of neutrophil infiltration and granulomatous inflammation at the site of infection. The present study examined the mechanisms by which B cells regulate the host neutrophilic response upon exposure to mycobacteria and how neutrophilia may influence vaccine efficacy. To address these questions, a murine aerosol infection tuberculosis (TB) model and an intradermal (ID) ear BCG immunization mouse model, involving both the μMT strain and B cell-depleted C57BL/6 mice, were used. IL (interleukin)-17 neutralization and neutrophil depletion experiments using these systems provide evidence that B cells can regulate neutrophilia by modulating the IL-17 response during M. tuberculosis infection and BCG immunization. Exuberant neutrophilia at the site of immunization in B cell-deficient mice adversely affects dendritic cell (DC) migration to the draining lymph nodes and attenuates the development of the vaccine-induced Th1 response. The results suggest that B cells are required for the development of optimal protective anti-TB immunity upon BCG vaccination by regulating the IL-17/neutrophilic response. Administration of sera derived from M. tuberculosis-infected C57BL/6 wild-type mice reverses the lung neutrophilia phenotype in tuberculous μMT mice. Together, these observations provide insight into the mechanisms by which B cells and humoral immunity modulate vaccine-induced Th1 response and regulate neutrophila during M. tuberculosis infection and BCG immunization.
Highlights
It has recently been demonstrated that B cells can shape the development of the immune response to Mycobacterium tuberculosis [1,2]
FccR knockout mouse studies suggest that humoral immunity can influence development of Th1 responses during M. tuberculosis infection [2]
The results generated in two different models involving mMT and C57BL/6 mice rendered B cell-deficient via treatment with two independent B cell-depleting agents, revealed B celldependent tissue neutrophilia at the site of interaction between mycobacteria and the host
Summary
It has recently been demonstrated that B cells can shape the development of the immune response to Mycobacterium tuberculosis [1,2]. The lungs of M. tuberculosis-infected B cell-deficient mice display exacerbated inflammation, with enhanced neutrophil recruitment [1]. Neutrophils are among the earliest cells to migrate to the site of M. tuberculosis infection and evidence exists that these phagocytes participate in the granulomatous reaction [3,4]. There is evidence suggesting that interaction of M. tuberculosis with neutrophils enhances DC migration to the draining lymph nodes thereby promoting the initiation of adaptive immune response in an aerogenic tuberculous infection [8]. Studies examining the significance of neutrophils in protection against M. tuberculosis have yielded conflicting results [3,5,9,10,11,12,13,14], and the role of these professional phagocytes in TB remains to be clearly defined
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