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.