Mast Cells Recruited to Mesenteric Lymph Nodes during Helminth Infection Remain Hypogranular and Produce IL-4 and IL-6

Abstract

Mast cells (MC) and basophils (Ba) share expression of the high affinity receptor for IgE (FcεRI) but can be distinguished by their divergent expression of KIT and CD49b. In BALB/c mice, MC lineage cells expressing high levels of FcεRI by flow cytometry were seen only in bone marrow (BM) while those expressing intermediate levels of FcεRI were present in BM and spleen of naïve mice and in mesenteric lymph nodes (mLN) of Trichinella spiralis-infected mice. These FcεRI+KIT+CD49b− cells had a membrane phenotype like intraperitoneal connective tissue-type MC, but were smaller and hypogranular by flow cytometry forward and side scatter profiles, respectively. Consistent with this, they lacked the prominent secretory granules identified by histochemistry and immunodetection for the MC-specific granule proteases that are readily seen in mature jejunal mucosal MC (MMC) that also are induced by the infection and present at the same time. The concentration of these MC lineage cells in mLN determined by flow cytometry was comparable to that of MC progenitors (MCp) measured by limiting dilution and clonal expansion with maturation. We observed upregulation of IL-4 mRNA levels by MCp in mLN and spleens of helminth-infected 4get mice, and demonstrated by intracellular cytokine staining production of IL-4 and IL-6 by the mLN MCp in helminth-infected mice. Furthermore, treatment of helminth-infected mice with anti-FcεRI mAb, a protocol known to deplete Ba, also depleted mLN MCp. Thus, this study identifies a hypogranular subset of MCp recruited to mLN by helminth infection that may be an important unrecognized source of cytokines.

Induction of Interleukin-9-Producing Mucosal Mast Cells Promotes Susceptibility to IgE-Mediated Experimental Food Allergy

“…Thus, the ability of murine strains to mount the intestinal CD4 + Th2 cell-mediated immune response to ingested dietary antigens, not their MHC H2 haplotype, correlated positively with MMC9 frequency, and consequently, susceptibility to food allergy. Whether our findings of MMC9s and its dependence on CD4 + Th2 cells pertain to helminth-induced T-cell dependent mucosal MCs and IL-9 dependence of the protective response to Trichinella spiralis infection remains to be investigated (Angkasekwinai et al, 2013; Dillon and MacDonald, 1986; Liu et al, 2013; Ruitenberg and Elgersma, 1976; Urban et al, 2000). …”

Mast Cells and Influenza A Virus: Association with Allergic Responses and Beyond

“…Finally, both prostaglandin E 2 and leukotriene B 4 (LTB 4 ), which can be highly produced by mast cells, have been shown to enhance chemotaxis of mast cell progenitors (58,59). In addition to their well-elucidated role in allergic airway disease, there is strong evidence for an accumulation of mast cells in the intestinal tract during helminth infections (60). Furthermore, mast cell precursors appear to accumulate at sites of viral infection including IAV, Sendai virus, infectious bursal disease virus (IBDV), and Newcastle disease virus (NDV) (61)(62)(63)(64)(65).…”

Two Functionally Distinct Subsets of Mast Cells Discriminated By IL-2–Independent CD25 Activities

“…Indeed, the protease repertoire of mast cells was strongly influenced by the surrounding host tissue (6), and Trichinella spiralis infection led to the identification of hypogranular mast cells that could be an important source of cytokines during helminth infection (7). Potentially, other mast cell subsets with different characteristics, possibly tailored to and determined by the local environment of a given tissue or inflammatory status, await description.…”