Accumulation of eosinophils in intestine‐draining mesenteric lymph nodes occurs after Trichuris muris infection

Abstract

Eosinophils have recently been demonstrated capable of localizing to lymph nodes that drain mucosal surfaces, in particular during T helper 2 (Th2) responses. Resistance of mice to infection with the gastrointestinal nematode Trichuris muris depends critically on mounting of a Th2 response and represents a useful model system to investigate Th2 responses. Following infection of resistant BALB/c mice with T. muris, we observed accumulation of eosinophils in intestine-draining mesenteric lymph nodes (MLNs). The accumulation of MLN eosinophils was initiated during the second week of infection and peaked during worm expulsion. In contrast, we detected a comparably late and modest increase in eosinophil numbers in the MLNs of infected susceptible AKR mice. MLN eosinophils localized preferentially to the medullary region of the lymph node, displayed an activated phenotype and contributed to the interleukin-4 (IL-4) response in the MLN. Despite this, mice genetically deficient in eosinophils efficiently generated IL-4-expressing CD4+ T cells, produced Th2 cytokines and mediated worm expulsion during primary T. muris infection. Thus, IL-4-expressing eosinophils accumulate in MLNs of T. muris-infected BALB/c mice but are dispensable for worm expulsion and generation of Th2 responses, suggesting a distinct or subtle role of MLN eosinophils in the immune response to T. muris infection.

Immunity to gastrointestinal nematode infections

“…There are little data, however, to suggest that deficiency in either IL-5 or eosinophils affects the polarization of protective immunity or by extension the outcome of infection, despite that eosinophil-derived mediators can skew dendritic cells to promote type 2 immunity. 83,84 Thus, eosinophils do not appear to be critical for the generation of T helper cell type 2 (Th2) immunity or clearance of T. muris, 85 and blocking IL-5 does not affect H. polygyrus expulsion despite significantly decreasing eosinophil numbers. 86 If anything, eosinophils act positively on the fecundity of H. polygyrus worms.…”

“…Interestingly, some studies suggest that ILC, 129-131 basophils, [132][133][134] and eosinophils 135,136 can express major histocompatibility complex class II and directly prime Th2 responses, notably upon N. brasiliensis 131 and T. muris 132 infections, with each cell type having been shown to migrate to the mesenteric lymph nodes during infection. 85,87,137,138 However, given that protective immunity is abolished in mice where all 139,140 or specific subsets 104-106,108,109 of dendritic cells have been depleted, it is perhaps more likely that these other innate cells contribute to local tissue immunity by promoting dendritic cell activation, or by further enhancing the cytokine response of mature T cells that have migrated to the infected tissue. 53 Moreover, dendritic cells are responsive not only to cytokines produced by other innate cells, but also to epithelium-derived cytokines, including TSLP, 54,[141][142][143] IL-25, 144 and IL-33, 52,145 thus potentially bypassing ILC2 and granulocytes entirely.…”

Immunobiology of Intestinal Eosinophils – A Dogma in the Changing?

“…Expression of CD11c and variation in the expression levels of Siglec-F and CD62L can be utilized to differ between the eosinophil populations in various tissues. Similar to intestinal eosinophils, those in the thymus, uterus and mesenteric lymph nodes (MLN) are CD11c + Siglec-F hi , whereas lung and blood eosinophils are CD11c -Siglec-F low (although other studies [9] report that lung eosinophils express high levels of Siglec-F) [6,10] . Fur thermore, while MLN and large intestinal eosinophils are CD62L low/-, blood eosinophils express high levels of CD62L [10] .…”

“…Similar to intestinal eosinophils, those in the thymus, uterus and mesenteric lymph nodes (MLN) are CD11c + Siglec-F hi , whereas lung and blood eosinophils are CD11c -Siglec-F low (although other studies [9] report that lung eosinophils express high levels of Siglec-F) [6,10] . Fur thermore, while MLN and large intestinal eosinophils are CD62L low/-, blood eosinophils express high levels of CD62L [10] . In summary, intestinal eosinophils are granular, CD45 + Siglec-F + CCR3 + CD11b + CD11c + Gr-1 int CD3 -c-kit -cells; in addition, while large intestinal eosinophils express F4/80, this must yet be clarified for small intestinal eosinophils.…”

“…However, ␤ 7 integrindeficient mice have normal numbers of SI eosinophils when in the steady state [22] , suggesting that ␣ 4 ␤ 7 is not required for eosinophil migration/retention in the small intestinal mucosa in the steady state. Apart from ␣ 4 ␤ 7, peripheral eosinophils also express ␤ 2 integrins when in the steady state, including ␣ L ␤ 2 (LFA-1) and ␣ M ␤ 2 (Mac-1) [10,23] , and the localization of eosinophils to the colonic mucosa when in the steady state is reduced in mice treated with antibodies towards the ␤ 2 integrin ligand ICAM-1 [23] ( fig. 1 ).…”