Basophils Are Dispensable for the Control of a Filarial Infection

Hartmann, Wiebke; Linnemann, Lara; Reitz, Martina; Specht, Sabine; Voehringer, David; Breloer, Minka

doi:10.4049/immunohorizons.1800018

Cited by 7 publications

(11 citation statements)

References 23 publications

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“…Basophils were also not required for the initiation of a Th2 response to Schistosoma mansoni in constitutive basophil-deficient Basoph8 x Rosa-DTa mice [27] or Mcpt8-Cre mice [28]. Moreover, Litomosoides sigmodontis infection, a model for human filarial infections [29] elicited comparable cellular and humoral immune responses and was cleared with similar kinetics in basophil-deficient Mcpt8-Cre mice and Mcpt8-WT mice [11].…”

Section: Discussionmentioning

confidence: 99%

“…We and others have shown that, although clearly contributing to the early expulsion of Strongyloides adults from the intestine, basophils play only a minor role in the final control and termination of infection [4, 7]. Also intestinal parasite burden during a primary infection with Nippostrongylus brasiliensis , Heligmosomoides polygyrus , Trichinella spiralis and Litomosoides sigmodontis were not affected by basophil deficiency or depletion [8–11]. However, several lines of evidence suggest a contribution of basophils in the generation and execution of the protective immune response during a secondary infection with N .…”

Section: Introductionmentioning

confidence: 99%

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Basophils are dispensable for the establishment of protective adaptive immunity against primary and challenge infection with the intestinal helminth parasite Strongyloides ratti

et al. 2018

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Infections with helminth parasites are controlled by a concerted action of innate and adaptive effector cells in the frame of a type 2 immune response. Basophils are innate effector cells that may also contribute to the initiation and amplification of adaptive immune responses. Here, we use constitutively basophil-deficient Mcpt8-Cre mice to analyze the impact of basophils during initiation and execution of the protective type 2 responses to both, a primary infection and a challenge infection of immune mice with the helminth parasite Strongyloides ratti. Basophil numbers expanded during parasite infection in blood and mesenteric lymph nodes. Basophil deficiency significantly elevated intestinal parasite numbers and fecal release of eggs and larvae during a primary infection. However, basophils were neither required for the initiation of a S. ratti-specific cellular and humoral type 2 immune response nor for the efficient protection against a challenge infection. Production of Th2 cytokines, IgG1 and IgE as well as mast cell activation were not reduced in basophil-deficient Mcpt8-Cre mice compared to basophil-competent Mcpt8-WT littermates. In addition, a challenge infection of immune basophil-deficient and WT mice resulted in a comparable reduction of tissue migrating larvae, parasites in the intestine and fecal release of eggs and L1 compared to mice infected for the first time. We have shown previously that S. ratti infection induced expansion of Foxp3+ regulatory T cells that interfered with efficient parasite expulsion. Here we show that depletion of regulatory T cells reduced intestinal parasite burden also in absence of basophils. Thus basophils were not targeted specifically by S. ratti-mediated immune evasive mechanisms. Our collective data rather suggests that basophils are non-redundant innate effector cells during murine Strongyloides infections that contribute to the early control of intestinal parasite burden.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Basophils are dispensable for the establishment of protective adaptive immunity against primary and challenge infection with the intestinal helminth parasite Strongyloides ratti

et al. 2018

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“…We have previously shown that IgE, that is known to activate mast cells by crosslinking of the high-affinity IgE receptor, is increased during L . sigmodontis infection as well [ 16 ]. Nevertheless, the absence of mast cells in Cpa3 cre mice did neither change the vascular permeability induced by blood-sucking mites nor the number of L4 or adult parasites in the thoracic cavity at any time point during L .…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, we have previously shown an increase of polyclonal IgE in the serum and an increase of L . sigmodontis -specific IgE locally in the thoracic cavity [ 16 ] until day 90 p.i. Thus, a repeated activation of mast cells during chronic L .…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2020

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Mast cells are innate effector cells that due to their localization in the tissue form the first line of defense against parasites. We have previously shown that specifically mucosal mast cells were essential for the termination of the intestinal Strongyloides ratti infection. Here, we analyze the impact of mast cells on the immune response and defense against the tissue-dwelling filarial nematode Litomosoides sigmodontis using mast cell-deficient Cpa3 cre mice. Despite an increase and an activation of mast cells at the site of infection in wildtype BALB/c mice the outcome of L . sigmodontis infection was not changed in mast cell-deficient BALB/c Cpa3 cre mice. In Cpa3 cre mice neither vascular permeability induced by blood-sucking mites nor the migration of L3 was altered compared to Cpa3 wildtype littermates. Worm burden in the thoracic cavity was alike in the presence and absence of mast cells during the entire course of infection. Although microfilaremiae in the peripheral blood increased in mast cell-deficient mice at some time points, the infection was cleared with comparable kinetics in the presence and absence of mast cells. Moreover, mast cell deficiency had no impact on the cytokine and antibody response to L . sigmodontis . In summary, our findings suggest that mast cells are not mandatory for the initiation of an appropriate immune response and host defense during L . sigmodontis infection in mice.

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Human filariasis—contributions of the Litomosoides sigmodontis and Acanthocheilonema viteae animal model

et al. 2021

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Filariae are vector-borne parasitic nematodes that are endemic worldwide, in tropical and subtropical regions. Important human filariae spp. include Onchocerca volvulus, Wuchereria bancrofti and Brugia spp., and Loa loa and Mansonella spp. causing onchocerciasis (river blindness), lymphatic filariasis (lymphedema and hydrocele), loiasis (eye worm), and mansonelliasis, respectively. It is estimated that over 1 billion individuals live in endemic regions where filarial diseases are a public health concern contributing to significant disability adjusted life years (DALYs). Thus, efforts to control and eliminate filarial diseases were already launched by the WHO in the 1970s, especially against lymphatic filariasis and onchocerciasis, and are mainly based on mass drug administration (MDA) of microfilaricidal drugs (ivermectin, diethylcarbamazine, albendazole) to filarial endemic areas accompanied with vector control strategies with the goal to reduce the transmission. With the United Nations Sustainable Development Goals (SDGs), it was decided to eliminate transmission of onchocerciasis and stop lymphatic filariasis as a public health problem by 2030. It was also requested that novel drugs and treatment strategies be developed. Mouse models provide an important platform for anti-filarial drug research in a preclinical setting. This review presents an overview about the Litomosoides sigmodontis and Acanthocheilonema viteae filarial mouse models and their role in immunological research as well as preclinical studies about novel anti-filarial drugs and treatment strategies.

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Basophils Are Dispensable for the Control of a Filarial Infection

Cited by 7 publications

References 23 publications

Basophils are dispensable for the establishment of protective adaptive immunity against primary and challenge infection with the intestinal helminth parasite Strongyloides ratti

Basophils are dispensable for the establishment of protective adaptive immunity against primary and challenge infection with the intestinal helminth parasite Strongyloides ratti

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

Human filariasis—contributions of the Litomosoides sigmodontis and Acanthocheilonema viteae animal model

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