Differences in the Importance of Mast Cells, Basophils, IgE, and IgG versus That of CD4⁺T Cells and ILC2 Cells in Primary and Secondary Immunity to Strongyloides venezuelensis

Abstract

There is evidence that mast cells, basophils, and IgE can contribute to immune responses to parasites; however, the relative levels of importance of these effector elements in parasite immunity are not fully understood. Previous work in Il3-deficient and c-kit mutant Kit W/W-v mice indicated that interleukin-3 and c-Kit contribute to expulsion of the intestinal nematode Strongyloides venezuelensis during primary infection. Our findings in mast cell-deficient Kit W-sh/W-sh mice and two types of mast cell-deficient mice that have normal c-kit ("Hello Kitty" and MasTRECK mice) confirmed prior work in Kit W/W-v mice that suggested that mast cells play an important role in S. venezuelensis egg clearance in primary infections. We also assessed a possible contribution of basophils in immune responses to S. venezuelensis. By immunohistochemistry, we found that numbers of basophils and mast cells were markedly increased in the jejunal mucosa during primary infections with S. venezuelensis. Studies in basophil-deficient Mcpt8 DTR mice revealed a small but significant contribution of basophils to S. venezuelensis egg clearance in primary infections. Studies in mice deficient in various components of immune responses showed that CD4 ϩ T cells and ILC2 cells, IgG, FcR␥, and, to a lesser extent, IgE and FcRI contribute to effective immunity in primary S. venezuelensis infections. These findings support the conclusion that the hierarchy of importance of immune effector mechanisms in primary S. venezuelensis infection is as follows: CD4 ϩ T cells/ILC2 cells, IgG, and FcR␥Ͼ mast cellsϾIgE and FcRIϾbasophils. In contrast, in secondary S. venezuelensis infection, our evidence indicates that the presence of CD4 ϩ T cells is of critical importance but mast cells, antibodies, and basophils have few or no nonredundant roles.

Mast Cells: Fascinating but Still Elusive after 140 Years from Their Discovery

“…Indeed, the last years have witnessed unprecedented progress in our understanding of the development of mast cells [40][41][42]. Moreover, extraordinary progress has been made in understanding the complex homeostatic and protective roles of these cells in different pathophysiological conditions [31,39,114,115]. Mast cells, known for decades for their detrimental role in allergic diseases, are now recognized to play crucial roles in a diverse array of physiological and pathologic functions [15,30,116].…”

“…For several decades mast cells were considered to play mainly proinflammatory roles in several allergic disorders, such as bronchial asthma [2][3][4]122], allergic rhinitis [5], urticaria [6,7], food allergy [8,9], anaphylaxis [10,11], atopic dermatitis [12], and angioedema [13]. During the last years, it became evident that mast cells represent an important cell during bacterial [26,27,29], fungal [29], viral [25,29], and helminth infections [30,31]. Elegant studies have demonstrated that mast cell-derived mediators can play protective roles against several venoms [114,115].…”

“…Moreover, these cells can be activated by different viral [25,26] and bacterial proteins [27,28] and thereby represent a potentially important cell during microbial infections. Therefore, the spectrum of diseases in which mast cells and their mediators have been implicated has extended to include bacterial, fungal, viral, and helminth infections [26,[29][30][31]; several diseases of the cardiovascular [14,32,33] and gastrointestinal systems [34][35][36]; and the joints [37,38]. Figure 1 schematically summarizes the wide spectrum of pathophysiological conditions in which mast cells and their mediators have been implicated during the last decades.…”

SHIP negatively regulates type II immune responses in mast cells and macrophages

“…However, mast cells employ the same strategy to confer protection against helminth parasites . In fact, IgE‐mediated mast cell induction of type 2 innate lymphoid cells is required for parasite control and expulsion . Recent studies have also demonstrated that mast cells play an important role in protection against arthropod and animal venoms.…”

Compartmentalized lymph node drainage dictates intestinal adaptive immune responses

“…larvae infect via the skin, and intestinal adult worm load peaks at 6-8 days post infection (p.i.) and is cleared after 10-12 days 22 . We observed that upon S.v.…”