Defined Intestinal Regions Are Drained by Specific Lymph Nodes That Mount Distinct Th1 and Th2 Responses Against Schistosoma mansoni Eggs

Mayer, Johannes U; Brown, Sheila; MacDonald, Andrew S.; Milling, Simon

doi:10.3389/fimmu.2020.592325

Cited by 20 publications

(11 citation statements)

References 68 publications

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“…To investigate whether there was an immune component to the loss of resistance to Tm infection in co‐infected mice we isolated the cMLN most proximal to the caecum (Figure 2A) from naive mice and infected groups at d3, d7, d14, and d20 post‐infection and enumerated the total number of cells present. In our experience this cMLN undergoes the most pronounced hyperplasia following Tm infection, suggesting it as the primary draining MLN for the caecum and/or proximal colon, this is supported by observations from other groups which demonstrate different regions of the intestines drain to specific MLNs 30,32 . As early as d3, mice mono‐infected with Tm displayed increased cellularity of the cMLN relative to naïve mice, with this becoming especially evident at d20 (Figure 2B).…”

Section: Resultssupporting

confidence: 82%

“…In our experience this cMLN undergoes the most pronounced hyperplasia following Tm infection, suggesting it as the primary draining MLN for the caecum and/or proximal colon, this is supported by observations from other groups which demonstrate different regions of the intestines drain to specific MLNs. 30,32 As early as d3, mice mono-infected with Tm displayed increased cellularity of the cMLN relative to naïve mice, with this becoming especially evident at d20 (Figure 2B). By contrast, coinfected mice showed no-increased cellularity of the cMLN at d3, d7, or d14, and whilst they significantly increased the total number of cMLN cells at d20, relative to uninfected controls, they had a significantly lower cell count than the Tm mono-infected group.…”

Section: Co-infection With H Bakeri Reduces Colonic Mln Cellularity B...mentioning

confidence: 99%

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Anti‐Trichuris mucosal responses are maintained during H. bakeri co‐infection despite impaired parasite expulsion

Colombo

Thompson

Bancroft

et al. 2022

Parasite Immunology

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In endemic regions concurrent infection with multiple gastrointestinal (GI) helminth species is more common than single species infection. However, the majority of model helminth infections focus on single species infections leading to a lack of understanding of how co‐infection influences anti‐parasite immune responses. Here, we use a model co‐infection of Trichuris muris (Tm) and Heligmosomoides bakeri (Hb) to investigate the effect of Hb on anti‐Tm immune responses. We observed a complete impairment of Tm expulsion in immune competent C57BL/6 mice when co‐infected with Hb. This was coupled with reduced cellularity in the colonic mesenteric lymph node (cMLN) proximal to the caecum, however, cMLN cytokine responses and caecal mucosal immune responses in co‐infected mice were not significantly different from mice infected with Tm alone. Interestingly, in immune‐compromised mice, we found co‐infection resulted in enhanced growth and fecundity of female Tm parasites. These data suggest that during helminth‐helminth co‐infection, immune‐independent signals between species may promote survival and growth.

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Section: Resultssupporting

confidence: 82%

Section: Co-infection With H Bakeri Reduces Colonic Mln Cellularity B...mentioning

confidence: 99%

Anti‐Trichuris mucosal responses are maintained during H. bakeri co‐infection despite impaired parasite expulsion

Colombo

Thompson

Bancroft

et al. 2022

Parasite Immunology

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“…These findings are supported by observations that basophils isolated from healthy human spleens showed no expression of HLA-DR or costimulatory molecules at steady state or after in vitro stimulation and could not drive T cell proliferation, indicating that human basophil function is restricted to the secretion of soluble mediators (89). However, other studies have suggested that basophils provide help to DC for optimal Th2 induction (75,90,91). As basophils are major producers of IL-4, while DC are not (92), basophils could provide an early source of IL-4 (93), especially in dLN (Figure 2C).…”

Section: Indirect Mechanisms Of Basophilenhanced Antigen Presentationsupporting

confidence: 53%

Basophils control T cell priming through soluble mediators rather than antigen presentation

Möbs

Salheiser²,

Bleise³

et al. 2023

Front. Immunol.

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Basophils play an important role in the development of type 2 immunity and have been linked to protective immunity against parasites but also inflammatory responses in allergic diseases. While typically classified as degranulating effector cells, different modes of cellular activation have been identified, which together with the observation that different populations of basophils exist in the context of disease suggest a multifunctional role. In this review we aim to highlight the role of basophils play in antigen presentation of type 2 immunity and focus on the contribution basophils play in the context of antigen presentation and T cell priming. We will discuss evidence suggesting that basophils perform a direct role in antigen presentation and relate it to findings that indicate cellular cooperation with professional antigen-presenting cells, such as dendritic cells. We will also highlight tissue-specific differences in basophil phenotypes that might lead to distinct roles in cellular cooperation and how these distinct interactions might influence immunological and clinical outcomes of disease. This review thus aims to consolidate the seemingly conflicting literature on the involvement of basophils in antigen presentation and tries to find a resolution to the discussion whether basophils influence antigen presentation through direct or indirect mechanisms.

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“…After long-term evolution in mammalian hosts, helminths have developed strategies to survive in the hostile immune environment. It has been shown that helminths have acquired the ability to modulate host immune responses, especially through skewing host immune response to the type-2/regulatory phenotype, in order to escape Th-1-based immune attack [ 21 , 22 , 23 ]. Macrophages play important roles in both innate immune responses and adaptive immunity, as one of the first lines of defense against pathogens [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

PD-L2 Blockade Exacerbates Liver Lesion in Mice Infected with Capillaria hepatica through Reducing Alternatively Activated Macrophages

Huang

Li²,

Zheng³

et al. 2023

TropicalMed

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Capillaria hepatica is a seriously neglected zoonotic parasite, which infects the liver of mammalian hosts, causing fibrosis or even hepatic failure. At present, the immune responses elicited by C. hepatica are not fully understood, and the role(s) of the programmed death 1 (PD-1) signaling pathway in the context of C. hepatica-induced pathology are not known. In this study, we identify that the late stage of infection with C. hepatica—especially the egg-derived antigens—modulates the host immune responses to promote alternatively activated macrophage (M2) polarization and programmed death ligand 2 (PD-L2) expression. The PD-L2-expressing alternatively activated M2 macrophages play an important role in maintaining Th2-biased regulatory immune responses, which may facilitate the survival of parasitic worms or eggs within the infected liver and reduce the liver pathology caused by the egg granulomas. Treatment with anti-PD-L2 antibody had no effect on the survival of parasitic eggs but deteriorated the pathology of egg granulomas. The obtained results suggest that PD-1/PD-L2 signaling, which is involved in alternative macrophage polarization, determines the immune response pattern and the immunopathology, consequently determining the outcome of the parasitic infection.

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Defined Intestinal Regions Are Drained by Specific Lymph Nodes That Mount Distinct Th1 and Th2 Responses Against Schistosoma mansoni Eggs

Abstract: uptake and priming characteristics of antigen-positive dendritic cell subsets and the site of infection, which shape the level of Th1 and Th2 responses in order to create a favorable immunological environment for the parasite.

Cited by 20 publications

References 68 publications

Anti‐Trichuris mucosal responses are maintained during H. bakeri co‐infection despite impaired parasite expulsion

Anti‐Trichuris mucosal responses are maintained during H. bakeri co‐infection despite impaired parasite expulsion

Basophils control T cell priming through soluble mediators rather than antigen presentation

PD-L2 Blockade Exacerbates Liver Lesion in Mice Infected with Capillaria hepatica through Reducing Alternatively Activated Macrophages

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