Limited role of mast cells during infection with the parasitic nematode Litomosoides sigmodontis

Linnemann, Lara; Reitz, Martina; Feyerabend, Thorsten B.; Breloer, Minka; Hartmann, Wiebke

doi:10.1371/journal.pntd.0008534

Cited by 9 publications

(5 citation statements)

References 24 publications

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“…Beneficial functions of mast cells and IgE are commonly invoked in parasite immunity 31 . However, parasite infections may be unperturbed 32 or only delayed in the absence of mast cells 33 , and functions of mast cells and IgE can be redundant with those of other cells (for instance, eosinophils 34 ) or antibody isotypes 35 , 36 . Given the complexities in understanding the actual roles of mast cells in immunological protection, the role for mast cells observed here in antigen-avoidance behaviour is intriguing.…”

Section: Discussionmentioning

confidence: 99%

Mast cells link immune sensing to antigen-avoidance behaviour

Plum

Binzberger

Thiele

et al. 2023

Nature

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The physiological functions of mast cells remain largely an enigma. In the context of barrier damage, mast cells are integrated in type 2 immunity and, together with immunoglobulin E (IgE), promote allergic diseases. Allergic symptoms may, however, facilitate expulsion of allergens, toxins and parasites and trigger future antigen avoidance1–3. Here, we show that antigen-specific avoidance behaviour in inbred mice4,5 is critically dependent on mast cells; hence, we identify the immunological sensor cell linking antigen recognition to avoidance behaviour. Avoidance prevented antigen-driven adaptive, innate and mucosal immune activation and inflammation in the stomach and small intestine. Avoidance was IgE dependent, promoted by Th2 cytokines in the immunization phase and by IgE in the execution phase. Mucosal mast cells lining the stomach and small intestine rapidly sensed antigen ingestion. We interrogated potential signalling routes between mast cells and the brain using mutant mice, pharmacological inhibition, neural activity recordings and vagotomy. Inhibition of leukotriene synthesis impaired avoidance, but overall no single pathway interruption completely abrogated avoidance, indicating complex regulation. Collectively, the stage for antigen avoidance is set when adaptive immunity equips mast cells with IgE as a telltale of past immune responses. On subsequent antigen ingestion, mast cells signal termination of antigen intake. Prevention of immunopathology-causing, continuous and futile responses against per se innocuous antigens or of repeated ingestion of toxins through mast-cell-mediated antigen-avoidance behaviour may be an important arm of immunity.

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Section: Discussionmentioning

confidence: 99%

Mast cells link immune sensing to antigen-avoidance behaviour

Plum

Binzberger

Thiele

et al. 2023

Nature

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“…Both low body condition (Gilot-Fromont et al, 2012;Martin et al, 2008;Warburton, Pearl, et al, 2016) and age (De Coster et al, 2010;Froy et al, 2019) anti-nematode immunity in their intestinal tract including eosinophils, mast cells and immunoglobulin A (Ezenwa et al, 2021). These immune mechanisms are known to be directly toxic and/or facilitate a type 2 immune response against worms (Linnemann et al, 2020;Obata-Ninomiya et al, 2020), potentially explaining why resistant hosts differ in nematode community similarity from non-resistant hosts. It is worth noting that the interaction between month of host capture and host age also had a significant effect on the adult nematode β diversity.…”

Section: Discussionmentioning

confidence: 99%

Within‐host and external environments differentially shape β‐diversity across parasite life stages

Warburton

Budischak

Jolles

et al. 2023

Journal of Animal Ecology

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Uncovering drivers of community assembly is a key aspect of learning how biological communities function. Drivers of community similarity can be especially useful in this task as they affect assemblage‐level changes that lead to differences in species diversity between habitats. Concepts of β‐diversity originally developed for use in free‐living communities have been widely applied to parasite communities to gain insight into how infection risk changes with local conditions by comparing parasite communities across abiotic and biotic gradients. Factors shaping β‐diversity in communities of immature parasites, such as larvae, are largely unknown. This is a key knowledge gap as larvae are frequently the infective life‐stage and understanding variation in these larval communities is thus key for disease prevention. Our goal was to uncover links between β‐diversity of parasite communities at different life stages; therefore, we used gastrointestinal nematodes infecting African buffalo in Kruger National Park, South Africa, to investigate within‐host and extra‐host drivers of adult and larval parasite community similarity. We employed a cross‐sectional approach using PERMANOVA that examined each worm community at a single time point to assess independent drivers of β‐diversity in larvae and adults as well as a longitudinal approach with path analysis where adult and larval communities from the same host were compared to better link drivers of β‐diversity between these two life stages. Using the cross‐sectional approach, we generally found that intrinsic, within‐host traits had significant effects on β‐diversity of adult nematode communities, while extrinsic, extra‐host variables had significant effects on β‐diversity of larval nematode communities. However, the longitudinal approach provided evidence that intrinsic, within‐host factors affected the larval community indirectly via the adult community. Our results provide key data for the comparison of community‐level processes where adult and immature stages inhabit vastly different habitats (i.e. within‐host vs. abiotic environment). In the context of parasitism, this helps elucidate host infection risk via larval stages and the drivers that shape persistence of adult parasite assemblages, both of which are useful for predicting and preventing infectious disease.

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“…Instead, the immune response relies on the binding of IgE to CD23 receptors found on eosinophils, platelets, macrophages, and dendritic cells. This leads to antigen presentation and the subsequent production of IgG antibodies ( 323 , 324 ). In contrast, mast cell degranulation may be induced without involving IgE ( 322 , 325 ).…”

Section: Physiologically Significant Functions Of Mast Cellsmentioning

confidence: 99%

Mast cell-mediated immune regulation in health and disease

Dileepan,

Raveendran,

Sharma

et al. 2023

Front. Med.

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Mast cells are important components of the immune system, and they perform pro-inflammatory as well as anti-inflammatory roles in the complex process of immune regulation in health and disease. Because of their strategic perivascular localization, sensitivity and adaptability to the microenvironment, and ability to release a variety of preformed and newly synthesized effector molecules, mast cells perform unique functions in almost all organs. Additionally, Mast cells express a wide range of surface and cytoplasmic receptors which enable them to respond to a variety of cytokines, chemicals, and pathogens. The mast cell’s role as a cellular interface between external and internal environments as well as between vasculature and tissues is critical for protection and repair. Mast cell interactions with different immune and nonimmune cells through secreted inflammatory mediators may also turn in favor of disease promoting agents. First and forefront, mast cells are well recognized for their multifaceted functions in allergic diseases. Reciprocal communication between mast cells and endothelial cells in the presence of bacterial toxins in chronic/sub-clinical infections induce persistent vascular inflammation. We have shown that mast cell proteases and histamine induce endothelial inflammatory responses that are synergistically amplified by bacterial toxins. Mast cells have been shown to exacerbate vascular changes in normal states as well as in chronic or subclinical infections, particularly among cigarette smokers. Furthermore, a potential role of mast cells in SARS-CoV-2-induced dysfunction of the capillary-alveolar interface adds to the growing understanding of mast cells in viral infections. The interaction between mast cells and microglial cells in the brain further highlights their significance in neuroinflammation. This review highlights the significant role of mast cells as the interface that acts as sensor and early responder through interactions with cells in systemic organs and the nervous system.

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Limited role of mast cells during infection with the parasitic nematode Litomosoides sigmodontis

Cited by 9 publications

References 24 publications

Mast cells link immune sensing to antigen-avoidance behaviour

Mast cells link immune sensing to antigen-avoidance behaviour

Within‐host and external environments differentially shape β‐diversity across parasite life stages

Mast cell-mediated immune regulation in health and disease

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