In vitro antigen presenting cell‐derived IL‐10 and IL‐6 correlate with Trichuris muris isolate‐specific survival

Abstract

Trichuris muris, the mouse whipworm, is used as a laboratory model of the human parasite T. trichiura. Three laboratory isolates of T. muris exist — the E, J and S isolates. Previous data have shown that the S isolate survives to chronicity in C57BL/6 mice unlike the E and J isolates, which are expelled. The ability of the S isolate to persist is thought to be due to it secreting unique excretory/secretory antigens, which interact with APCs such that protective T cell responses do not develop. To determine whether APCs respond differently to E/S antigens from the three isolates we cultured isolate-specific E/S with bone marrow-derived macrophages (BMMΦ) and dendritic cells (BMDCs) in vitro. Markers of co-stimulation and levels of MHC-II were analysed by FACS and cytokine levels in supernatants quantified. E/S antigens from the S isolate consistently stimulated significantly higher levels of IL-10 and IL-6 from both macrophages (F4/80+CD11b+CD11c−) and dendritic cells (CD11c+CD11b+F4/80−) compared to J and E isolate E/S. If these in vitro differences in APC-derived cytokines, particularly IL-10, are biologically significant in vivo, they may contribute to the S isolate survival, by creating a regulatory cytokine environment in which protective immune responses are less effective.

Whipworm Infection Promotes Bacterial Invasion, Intestinal Microbiota Imbalance, and Cellular Immunomodulation

“…Little is known about the effects of ES products from T. muris on immune cells. D'Elia and Else showed that the ES products from T. muris stimulate the secretion of IL-10 and IL-6 from bone marrow-derived macrophages and dendritic cells (47). It was shown here, for the first time, that the ES products of this nematode inhibit the inflammatory response of macrophages stimulated with bacterial LPS.…”

Exposure to Titanium Dioxide Nanomaterials Provokes Inflammation of an in Vitro Human Immune Construct

“…As seen in vivo , a balanced cytokine response is recapitulated in the PTE with the secretion of immunosuppressive cytokines like IL-10. The production of the immunosuppressive cytokine IL-10 by the resident phagocytic population in the PTE is likely an inflammatory mediator response to the increasing levels of IL-1 and TNFα 29,30. The cytokine/chemokine data illustrate that nanoscale TiO 2 of different structures and associated surface chemistries induce an inflammatory response in the PTE construct.…”

Protection and pathology during parasite infection: IL‐10 strikes the balance

“…IL‐10 activates the mastocytosis that is essential for the rapid expulsion of Trichinella spiralis , for example . IL‐10 remains immunosuppressive in the Th2 context, acting either to promote host‐protective Th2 development by shutting down Th1 potential or to protect the pathogen by disabling inflammatory responses that would otherwise cause expulsion . Interestingly, even in helminth infection, il10 deficiency can still associate with intense inflammation and consequent pathology: during Trichuris muris infection, for example, the absence of IL‐10 causes severe and sometimes fatal inflammation of the caecum .…”