Neutrophils Clear Bacteria Associated with Parasitic Nematodes Augmenting the Development of an Effective Th2-Type Response

Abstract

Infection with the parasitic nematode Nippostrongylus brasiliensis induces a potent Th2 response; however, little is known about early stages of the innate response that may contribute to protective immunity. To examine early events in this response, chemokine expression in the draining lymph node was examined after N. brasiliensis inoculation. Pronounced increases of several chemokines, including CCL2, were observed. Compared with wild-type mice, elevations in a Gr-1bright population in the draining lymph node was significantly decreased in CCL2−/− mice after N. brasiliensis inoculation. Further flow cytometric and immunofluorescent analysis showed that in wild-type mice, Gr-1+ cells transiently entered and exited the draining lymph node shortly after N. brasiliensis inoculation. The Gr-1bright population was comprised of neutrophils expressing TGF-β and TNF-α. Following Gr-1+ cell depletion, N. brasiliensis infection resulted in transient, but significantly increased levels of IFN-γ, increased serum IgG2a, reduced Th2 cytokines and serum IgE, greatly increased mortality, and delayed worm expulsion. Furthermore, bacteria were readily detected in vital organs. Infection of Gr-1+ cell-depleted mice with N. brasiliensis larvae that were pretreated with antibiotics prevented bacterial dissemination, Th1 inflammatory responses, and decreases in host survival. This study indicates that parasitic nematodes can be an important vector of potentially harmful bacteria, which is typically controlled by CCL2-dependent neutrophils that ensure the optimal development of Th2 immune responses and parasite resistance.

IL-17 and neutrophils: unexpected players in the type 2 immune response

“…This is consistent with previous reports in allergy models in which type 2 cytokines are reduced in IL-17 deficient mice relative to wildtype animals [52,53]. This suggests paradoxically that IL-17 promotes type 2 responses, supported by reports in which neutrophils contribute to the subsequent type 2 response during N. brasiliensis infection [44,54]. However, as discussed below, in this same nematode model Th2 cytokines suppress IL-17A in the lung [26 ], as also reported by others [55 ,56].…”

Allergen-sensitization in vivo enhances mast cell-induced inflammatory responses and supports innate immunity

“…In this context our results show that allergic animals develop an effective and improved innate immune response to clear bacteria from peritoneum. This is consistent with the studies in parasitic nematode infected animals, another model of potent and highly polarized T H 2-type response, which demonstrate that neutrophils successfully clear bacteria associated with parasite nematode infections [29]. So, in conditions of T H 2 preferential polarization, animals may defend from bacterial infections supporting their innate immune response.…”

Neutrophils Exhibit Differential Requirements for Homing Molecules in Their Lymphatic and Blood Trafficking into Draining Lymph Nodes

“…For many years, it was thought that emigration from tissues was only confined to lymphocytes and DCs, but not to granulocytes. Nevertheless, we and others have shown that neutrophils can migrate to LNs in response to different stimuli, such as inflammation (12)(13)(14) or infection (15)(16)(17)(18), where they shape the immune response by interacting with DCs and hence modulating Ag presentation (19). Indeed, we previously reported that, when OVA Ag is injected into hind footpads of previously OVA/CFA-immunized mice, the main OVA + cells in footpads and popliteal LNs (poLNs) are neutrophils (12).…”