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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 share expression of the high-affinity receptor for IgE (Fc?RI) but can be distinguished by their divergent expression of KIT and CD49b. In BALB/c mice, MC lineage cells expressing high levels of Fc?RI by flow cytometry were seen only in bone marrow whereas those expressing intermediate levels of Fc?RI were present in bone marrow and spleen of naive mice and in mesenteric lymph nodes (mLN) of Trichinella spiralis-infected mice. These Fc?RI(+)KIT(+)CD49b(-) cells had a membrane phenotype similar to i.p. 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 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 transcription by MCp in mLN and spleens of helminth-infected 4get mice, and we 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-Fc?RI mAb, a protocol known to deplete basophils, 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.

SUBMITTER: Liu AY

PROVIDER: S-EPMC3563837 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

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Mast cells recruited to mesenteric lymph nodes during helminth infection remain hypogranular and produce IL-4 and IL-6.

Liu Anne Y AY Dwyer Dan F DF Jones Tatiana G TG Bankova Lora G LG Shen Shiliang S Katz Howard R HR Austen K Frank KF Gurish Michael F MF

Journal of immunology (Baltimore, Md. : 1950) 20130114 4

Mast cells (MC) and basophils 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 whereas those expressing intermediate levels of FcεRI were present in bone marrow and spleen of naive mice and in mesenteric lymph nodes (mLN) of Trichinella spiralis-infected mice. These FcεRI(+)KIT(+)CD49b(-) cells had ...[more]

PMID: 23319739

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Project description:BACKGROUND: Prion diseases are characterized by the accumulation of the pathogenic PrPSc protein, mainly in the brain and the lymphoreticular system. Although prions multiply/accumulate in the lymph nodes without any detectable pathology, transcriptional changes in this tissue may reflect biological processes that contribute to the molecular pathogenesis of prion diseases. Little is known about the molecular processes that occur in the lymphoreticular system in early and late stages of prion disease. We performed a microarray-based study to identify genes that are differentially expressed at different disease stages in the mesenteric lymph node of sheep naturally infected with scrapie. Oligo DNA microarrays were used to identify gene-expression profiles in the early/middle (preclinical) and late (clinical) stages of the disease. RESULTS: In the clinical stage of the disease, we detected 105 genes that were differentially expressed (?2-fold change in expression). Of these, 43 were upregulated and 62 downregulated as compared with age-matched negative controls. Fewer genes (50) were differentially expressed in the preclinical stage of the disease. Gene Ontology enrichment analysis revealed that the differentially expressed genes were largely associated with the following terms: glycoprotein, extracellular region, disulfide bond, cell cycle and extracellular matrix. Moreover, some of the annotated genes could be grouped into 3 specific signaling pathways: focal adhesion, PPAR signaling and ECM-receptor interaction. We discuss the relationship between the observed gene expression profiles and PrPSc deposition and the potential involvement in the pathogenesis of scrapie of 7 specific differentially expressed genes whose expression levels were confirmed by real time-PCR. CONCLUSIONS: The present findings identify new genes that may be involved in the pathogenesis of natural scrapie infection in the lymphoreticular system, and confirm previous reports describing scrapie-induced alterations in the expression of genes involved in protein misfolding, angiogenesis and the oxidative stress response. Further studies will be necessary to determine the role of these genes in prion replication, dissemination and in the response of the organism to this disease.

Dataset Information

Mast cells recruited to mesenteric lymph nodes during helminth infection remain hypogranular and produce IL-4 and IL-6.

Publications

Mast cells recruited to mesenteric lymph nodes during helminth infection remain hypogranular and produce IL-4 and IL-6.

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