Mucosal mast cells are indispensable for the timely termination of Strongyloides ratti infection

Abstract

Mast cells and basophils are innate immune cells with overlapping functions that contribute to anti-helminth immunity. Mast cell function during helminth infection was previously studied using mast cell-deficient Kit-mutant mice that display additional mast cell-unrelated immune deficiencies. Here, we use mice that lack basophils or mucosal and connective tissue mast cells in a Kit-independent manner to re-evaluate the impact of each cell type during helminth infection. Neither mast cells nor basophils participated in the immune response to tissue-migrating Strongyloides ratti third-stage larvae, but both cell types contributed to the early expulsion of parasitic adults from the intestine. The termination of S. ratti infection required the presence of mucosal mast cells: Cpa3 mice, which lack mucosal and connective tissue mast cells, remained infected for more than 150 days. Mcpt5 R-DTA mice, which lack connective tissue mast cells only, and basophil-deficient Mcpt8 mice terminated the infection after 1 month with wild-type kinetics despite their initial increase in intestinal parasite burden. Because Cpa3 mice showed intact Th2 polarization and efficiently developed protective immunity after vaccination, we hypothesize that mucosal mast cells are non-redundant terminal effector cells in the intestinal epithelium that execute anti-helminth immunity but do not orchestrate it.

Multifaceted roles of basophils in health and disease

“…Basophils also show some contribution in mice to the protective immunity in primary infection with Strongyloides ratti or Strongyloides venezuelensis. 82,83 In mice infected with other helminths, such as Trichuris muris or Trichinella spiralis, TSLP-elicited basophils play an important role in T H 2 responses to primary infection. 7,84 Bacterial infection B cells in the human upper respiratory mucosa generate local and circulating plasmablasts producing IgD reactive to respiratory bacteria, such as Moraxella catarrhalis and Haemophilus influenzae.…”

Killer Immunoglobulin-Like Receptor 2DL4 (CD158d) Regulates Human Mast Cells both Positively and Negatively: Possible Roles in Pregnancy and Cancer Metastasis

“…Mast cells play important roles in both innate and adaptive immune responses by secreting these mediators [4][5][6]. Studies using mast cell-deficient mice, such as Kit W/Wv mice and Kit Wsh/Wsh mice, revealed that mast cells protect against parasitic infections including Strongyloides ratti and Strongyloides brasiliensis [7,8], as well as the venoms of honeybees or vipers [9]. Mast cells are (KIR) 2DL4 [19][20][21][22][23][24][25][26][27][28][29][30][31].…”

Basophils Are Dispensable for the Control of a Filarial Infection

“…In summary, combined data from others and us provide accumulating evidence that basophils increase at the site of most helminth infections. However, despite their role in the initiation and execution of antihelminth immune responses during a first infection with some helminth species (7,22), basophils are dispensable during infection with the tissue-dwelling nematode L. sigmodontis. Therefore, our study highlights that nematodespecific differences exist, and it is not valid to draw general conclusions about the function of basophils during helminth infections from single studies.…”

“…Thus, most studies focused on the role of basophils in gastrointestinal nematode infection (6). In this context, we have shown that basophils are dispensable for the control of the tissue-migrating Strongyloides ratti L3 during primary infection and contribute to the control of parasitic adults in the intestine at the peak of infection (7). In other primary gastrointestinal infections, no obvious effector functions have been described for basophils (5).…”