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

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.

A crosstalk between type 2 innate lymphoid cells and alternative macrophages in lung development and lung diseases (Review)

“…Interleukin (IL)-4, IL-5, IL-9 and IL-13 are important cytokines that play key roles in type 2 immunity, and are usually involved in allergic diseases or during helminthic parasitic infections (8,9). Th2 cells and certain myeloid cells are considered the primary source of these type 2 cytokines (10,11); however, recent studies have reported that a rare subpopulation of innate lymphocytes are the predominant source (12)(13)(14).…”

TLR2 Regulates Mast Cell IL-6 and IL-13 Production During Listeria monocytogenes Infection

“…IL-13 together with IL-4, IL-5 and IL-10 belong to the group of cytokines of the type 2 response profile, since they promote the induction of the humoral immune response by favoring the production of antibodies by B cells, diminish the cellular immune response and lead to an anti-inflammatory environment (74,75). The type response profile 2 cytokines and other mediators produced by MC are able to direct, amplify and perpetuate the Th2 immune response in allergy, helminthic infection and in oral immunization models (76)(77)(78)(79)(80). Interestingly type 2 response has been recently associated as a relevant mechanism during bacterial infection, in particular during the skin infection with S. aureus, by favoring IgE production and effector mechanisms regulated by MC (81).…”

How to train your myeloid cells: a way forward for helminth vaccines?

“…In this model, mast cells continue accumulating in the mucosa and actively secrete proteases for more than 28 days after the expulsion of T. muris from the intestine ( 40 , 41 ). Mast cell-dependent expulsion has also been reported for the rat tapeworm H. diminuta using Kit W-sh -deficient mice that displayed delayed worm expulsion ( 42 ). Similarly, mast cells have been shown to be essential for adult expulsion using a novel model of mast cell deficiency (in Cpa3-Cre mice) that does not affect basophil number, contrary to c-kit -deficient mice ( 43 ).…”