Abstract
How B cells contribute to protective immunity against parasitic nematodes remains unclear, with their importance as accessory cells underexplored. In this study, anti-CD20 monoclonal antibody (α-CD20 mAb)-mediated depletion of B cells from C57BL/6 mice revealed an important role for B cells in supporting Th2 immune responses and thus expulsion of Trichuris muris (T. muris). C57BL/6 mice normally mount mixed Th1/Th2 immune responses to T. muris and expel the parasite by the third week post infection. However, B cell-depleted C57BL/6 had significantly reduced Th2-type cytokines post infection and failed to expel the parasite. IFN-γ production in the MLN of C57BL/6 mice receiving α-CD20 mAb treatment was not affected, collectively resulting in an overall change in Th1/Th2 balance in favor of Th1. Further, the expression of IFN-γ and IFN-γ-induced genes at the effector site, the gut, was significantly increased in the absence of B cells. Interestingly, and in complete contrast, BALB/c mice, which mount strongly polarized Th2 immune responses, rather than mixed Th1/Th2 immune responses, were still able to expel T. muris in the absence of B cells. We thus hypothesized that the B cell plays a critical role in enabling strong Th2 responses in the context of mixed Th1/Th2 settings, with the role becoming redundant in highly Th2 polarized environments. In support of this, neutralization of IFN-γ in B cell depleted C57BL/6 restored resistance against T. muris infection. Thus, our data suggest an important role of B cells in supporting Th2-type immune responses in mixed IFN-γ-rich Th1/Th2 settings.
Highlights
Infecting over two billion people around the world, mostly in resource-limited countries, the ability of parasitic helminths to maintain long-standing chronic infections makes them a major health care issue [1]
C57BL/6 Mice Treated With α-CD20 mAb Fail to Expel T. muris by d35 p.i., Correlating With an Absence of Class-Switched Antibodies and a Significant Decrease in Th2 Cytokines in the Mesenteric lymph nodes (MLNs)
To investigate whether B cells are important in resistance to T. muris during a primary infection of C57BL/6 mice, mice were treated with α-CD20 mAb 7 days prior to infection and again at 10 days p.i., given that a single α-CD20 mAb treatment failed to ablate B cells for the full duration of T. muris infection (Supplementary Figure 1)
Summary
Infecting over two billion people around the world, mostly in resource-limited countries, the ability of parasitic helminths to maintain long-standing chronic infections makes them a major health care issue [1]. Trichuris trichiura (T. trichiura) is one of the most common gastrointestinal nematodes, infecting ∼465 million people worldwide [2]. B Cells and Immunity to Trichuris muris with malnutrition, growth stunting, and reduced educational performance, whereas in adults, it is related to anemia, reduced worker productivity, and, in women, low-birth-weight babies [3]. Trichuris parasites secrete a heterogeneous array of molecules collectively referred to as the excretome/secretome (E/S), which can stimulate the host immune system [6, 7]. Infection of mice with the intestinal nematode parasite T. muris drives polarized T helper cell (Th) responses, which associate with resistance (Th2) or susceptibility (Th1) [4]. The key cellular contributions that support Th2 cell polarization during T. muris infection remain unclear. B cell function is related to antibody production, with B cells acting as antigen-presenting cells (APCs) [8,9,10] and as accessory cells, through their ability to secrete multiple cytokines [11]
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