Critical roles of regulatory B and T cells in helminth parasite-induced protection against allergic airway inflammation

The prevalence of allergic asthma and incidences of helminth infections in humans are inversely correlated. Although experimental studies have established the causal relation between parasite infection and allergic asthma, the mechanism of the parasite-associated immunomodulation is not fully elucidated. Using a murine model of asthma and nematode parasite Heligmosomoides polygyrus, we investigated the roles of regulatory B cells (B-reg) and T cells (T-reg) in mediation of the protection against allergic asthma by parasite. H. polygyrus infection significantly suppressed ovalbumin (OVA)-induced allergic airway inflammation (AAI) evidenced by alleviated lung histopathology and reduced numbers of bronchoalveolar inflammatory cell infiltration, and induced significant responses of interleukin (IL)-10(+) B-reg, IL-10(+) T-reg and forkhead box protein 3 (FoxP3)(+) T-reg in mesenteric lymph node and spleen of the mice. Adoptive transfer of IL-10(+) B-reg and IL-10(+) T-reg cell prevented the lung immunopathology in AAI mice. Depletion of FoxP3(+) T(reg )cells in FoxP3-diphtheria toxin (DT) receptor transgenic mice by diphtheria toxin (DT) treatment exacerbated airway inflammation in parasite-free AAI mice and partially abrogated the parasite-induced protection against AAI. IL-10(+) B-reg cells were able to promote IL-10(+) T-reg expansion and maintain FoxP3(+) T-reg cell population. These two types of T-regs failed to induce CD19(+) B cells to transform into IL-10(+) B-reg cells. These results demonstrate that B-reg, IL-10(+) T-reg and FoxP3(+) T-reg cells contribute in A discrepant manner to the protection against allergic airway immunopathology by parasiteS. B-reg cell might be a key upstream regulatory cell that induces IL-10(+) T-reg response and supports FoxP3(+) T-reg cell population which, in turn, mediate the parasite-imposed immunosuppression of allergic airway inflammation. These results provide insight into the immunological relationship between parasite infection and allergic asthma.