Abstract
Defining the immune mechanisms underlying protective immunity to helminth infection remains an important challenge. Here we report that lung CD4(+) T cells and Group 2 innate lymphoid cells (ILC2s) work in concert to block Nippostrongylus brasiliensis (Nb) development in the parenchyma within 48 h in mice. Immune-damaged larvae have a striking morphological defect that is dependent on the expansion of IL-13-producing ILC2 and CD4(+) T cells, and the activation of M2 macrophages. This T-cell requirement can be bypassed by administration of IL-2 or IL-33, resulting in expansion of IL-13-producing ILC2s and larval killing. Depletion of ILC2s inhibits larval killing in IL-2-treated mice. Our results broaden understanding of ILC2's role in immunity to helminths by demonstrating that they not only act as alarmin sensors, but can also be sustained by CD4(+) T cells, ensuring both the prompt activation and the maintenance of IL-13-dependent M2 macrophage immunity in the lung.
Highlights
Defining the immune mechanisms underlying protective immunity to helminth infection remains an important challenge
We show that either IL-33- or IL-2-directed activation of ILC2s is sufficient to stimulate M2-mediated reduction of worm burden in the lungs, while in the context of naturally acquired immunity cooperation between ILC2s and CD4 þ T cells is required for maintenance of anamnestic immunity
The expansion of ILC2s and the associated larval killing in Rag[1] À / À mice treated with IL-2C was abrogated by in vivo depletion with anti-CD90 antibody indicating a role for ILC2s in protection (Fig. 5j,k). These results indicate the potential role of IL-13producing ILC2s in mediating protective immunity against Nippostrongylus brasiliensis (Nb) albeit under the tight regulation by the cytokines IL-33 or IL-2 resulting from tissue damage or CD4 þ T-cell activation, respectively
Summary
Defining the immune mechanisms underlying protective immunity to helminth infection remains an important challenge. An important associated feature of Nb infection is the significant damage to the epithelium and vasculature of the lung resulting from worm penetration and subsequent migration through the parenchyma into the airways[2,9]. Activated macrophages[11] (M2) play a role in repairing the damage caused by Nb migration in the lung, both in the control of the initial haemorrhaging seen in the acute phase, and in the development of fibrosis and emphysema seen in the chronic phase[12], as well as having a potential role in anamnestic immunity against Nb. Group 2 innate lymphoid cells (ILC2) have been shown to be critical for the interleukin (IL)-9-dependent repair of lungs damaged by Nb infection[13]. The role of ILC2s in protective immunity against helminths has been extensively studied with gut-associated ILC2s shown to promote the weep and sweep expulsion of helminths from the small intestine[14,15]; the role of ILC2s in lung immunity against helminth infection, and their role in the potentiation of adaptive immunity, is unresolved
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