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Role of mast cells in the generation of a T‐helper type 2 dominated anti‐helminthic immune response

Ryan, Nathan M., Oghumu, Steve·2019·Bioscience Reports
DOI 10.1042/bsr20181771PMC PMC6379226
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Abstract

Mast cells are long-lived, innate immune cells of the myeloid lineage which are found in peripheral tissues located throughout the body, and positioned at the interface between the host and the environment. Mast cells are found in high concentrations during helminth infection. Using Kitw-sh mast cell deficient mice, a recently published study in Bioscience Reports by Gonzalez et al. (Biosci. Rep., 2018) focused on the role of mast cells in the immune response to infection by the helminth Hymenolepis diminuta. The authors showed that mast cells play a role in the modulation of Th2 immune response characterized by a unique IL-4, IL-5 and IL-13 cytokine profile, as well as subsequent robust worm expulsion during H. diminuta infection. Unlike WT mice which expelled H. diminuta at day 10, Kitw-sh deficient mice displayed delayed worm expulsion (day 14 post infection). Further, a possible role for mast cells in the basal expression of cytokines IL-25, IL-33 and thymic stromal lymphopoietin was described. Deletion of neutrophils in Kitw-sh deficient mice enhanced H. diminuta expulsion, which was accompanied by splenomegaly. However, interactions between mast cells and other innate and adaptive immune cells during helminth infections are yet to be fully clarified. We conclude that the elucidation of mechanisms underlying mast cell interactions with cells of the innate and adaptive immune system during infection by helminths can potentially uncover novel therapeutic applications against inflammatory, autoimmune and neoplastic diseases.

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Figure 1 Proposed mechanism for the action of mast cells during the immunological response to helminth infection by Hymenolepis diminuta Mast cells stimulate intestinal epithelial cells causing a constitutive expression of basal IL-25, IL-33 and TSLP. The presence of these cytokines in the intestinal lumen is crucial to an efficient immune response required for timely expulsion of helminths. Detection of helminths by the epithelial cells cause an increased release of cytokines IL-25, IL-33 and TSLP, resulting in the activation of mast cells and other Th2 lymphoid and myeloid progenitors. Mast cells secrete a wide variety of cytokines and growth factors including IL-4, IL-5, IL-13, IL-25, IL-33, TNF-α, CXCL1, CXCL2, and TSLP, MCPT-1, prostaglandin D2, and lysozyme. CXCL1, CXCL2 and TNF-α activates neutrophils, prostaglandin D2 production activates type 2 innate lymphoid cells, while IL-4, IL-5 and IL-13 activates alternatively activated macrophages. Mast cell derived IL-25 stimulates the Th2 immune response. Further, mast cell degranulation results in anti-helminthic effector mechanisms including goblet cell hyperplasia, increased mucin production, smooth muscle contraction and increased peristalsis, leading to helminth expulsion.
Figure 1 Proposed mechanism for the action of mast cells during the immunological response to helminth infection by Hymenolepis diminuta Mast cells stimulate intestinal epithelial cells causing a constitutive expression of basal IL-25, IL-33 and TSLP. The presence of these cytokines in the intestinal lumen is crucial to an efficient immune response required for timely expulsion of helminths. Detection of helminths by the epithelial cells cause an increased release of cytokines IL-25, IL-33 and TSLP, resulting in the activation of mast cells and other Th2 lymphoid and myeloid progenitors. Mast cells secrete a wide variety of cytokines and growth factors including IL-4, IL-5, IL-13, IL-25, IL-33, TNF-α, CXCL1, CXCL2, and TSLP, MCPT-1, prostaglandin D2, and lysozyme. CXCL1, CXCL2 and TNF-α activates neutrophils, prostaglandin D2 production activates type 2 innate lymphoid cells, while IL-4, IL-5 and IL-13 activates alternatively activated macrophages. Mast cell derived IL-25 stimulates the Th2 immune response. Further, mast cell degranulation results in anti-helminthic effector mechanisms including goblet cell hyperplasia, increased mucin production, smooth muscle contraction and increased peristalsis, leading to helminth expulsion.CC BY · PubMed Central

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Metadata

Authors
Ryan, N. M., & Oghumu, S.
Affiliations
Department of Pathology, College of Medicine, Ohio State University Wexner Medical Center, Columbus, OH, U.S.A.
ORCID
Oghumu, Steve
Venue
Bioscience Reports
Publisher
Portland Press Ltd.
Published
2019-02
Volume
39
Issue
2
ISSN
  • 0144-8463
  • 1573-4935
DOI
10.1042/bsr20181771
PMC
PMC6379226
Cited by
15
References
1
Language
en
Licence
creativecommons.org/licenses/by/4.0/ (vor, 220 d)

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