The skin is an important bulwark of acquired immunity against intestinal helminths

Obata-Ninomiya, Kazushige; Ishiwata, Kenji; Tsutsui, Hidemitsu; Nei, Yuichiro; Yoshikawa, Seiji; Kawano, Yoshiaki; Minegishi, Yoshiyuki; Ohta, Nobuhiro; Watanabe, Naohiro; Kanuka, Hirotaka; Karasuyama, Hajime

doi:10.1084/jem.20130761

Cited by 128 publications

(164 citation statements)

References 56 publications

(95 reference statements)

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“…Arginase 1 produced by M2-type macrophages is involved in the larval trapping in the skin. Depletion of either basophils or M2-type macrophages abolishes the larval trapping in the skin, but it has no significant impact on eosinophil accumulation in the infected skin (36). As shown in Fig.…”

Section: δDblgata Mice Show Impaired Acquired Protection Against Helmmentioning

confidence: 75%

“…Mice were first injected s.c. with 500 third-stage larvae (L3) of N. brasiliensis in the back, and 18 d later, they were injected intradermally with 500 L3 in the flank. Two days after the second larva inoculation, the skin of the inoculation site was isolated, and subjected to numerical counts of skin-trapped larvae and skin-infiltrating cells as described previously (36).…”

Section: Methodsmentioning

confidence: 99%

“…We then investigated whether the numerical and functional aberrancy of basophils in ΔdblGATA mice indeed has any significant impact on in vivo immune responses. We have recently demonstrated that basophils but not eosinophils play a key role in the protection against reinfection of an intestinal helminth Nippostrongylus brasiliensis by means of restraining infectious larvae from migration out of their entry point in the skin toward the lung and intestine (36). IgE-armed basophils recruited to the skin lesions of the second larval infection are activated in response to N. brasiliensis antigens to secrete IL-4, which in turn acts on monocytes/macrophages to promote their differentiation into M2-type macrophages in the skin.…”

Section: δDblgata Mice Show Impaired Acquired Protection Against Helmmentioning

confidence: 99%

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GATA-1 regulates the generation and function of basophils

Nei¹,

Obata-Ninomiya²,

Tsutsui³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Developmental processes of hematopoietic cells are orchestrated by transcriptional networks. GATA-1, the founding member of the GATA family of transcription factors, has been demonstrated to play crucial roles in the differentiation of erythroid cells, magakaryocytes, eosinophils, and mast cells. However, the role of GATA-1 in basophils remains elusive. Here we show that basophils abundantly express Gata1 mRNAs, and that siRNA-mediated knockdown of Gata1 resulted in impaired production of IL-4 by basophils in response to the stimulation with IgE plus antigens. ΔdblGATA mice that carry the mutated Gata1 promoter and are widely used for functional analysis of eosinophils owing to their selective loss of eosinophils showed a decreased number of basophils with reduced expression of Gata1 mRNAs. The number of basophil progenitors in bone marrow was reduced in these mice, and the generation of basophils from their bone marrow cells in culture with IL-3 or thymic stromal lymphopoietin was impaired. ΔdblGATA basophils responded poorly ex vivo to stimulation with IgE plus antigens compared with wild-type basophils as assessed by degranulation and production of IL-4 and IL-6. Moreover, ΔdblGATA mice showed impaired responses in basophil-mediated protective immunity against intestinal helminth infection. Thus, ΔdblGATA mice showed numerical and functional aberrancy in basophils in addition to the known deficiency of eosinophils. Our findings demonstrate that GATA-1 plays a key role in the generation and function of basophils and underscore the need for careful distinction of the cell lineage responsible for each phenotype observed in ΔdblGATA mice.

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Section: δDblgata Mice Show Impaired Acquired Protection Against Helmmentioning

confidence: 75%

Section: Methodsmentioning

confidence: 99%

Section: δDblgata Mice Show Impaired Acquired Protection Against Helmmentioning

confidence: 99%

See 1 more Smart Citation

GATA-1 regulates the generation and function of basophils

Nei¹,

Obata-Ninomiya²,

Tsutsui³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…It has been shown that basophils cooperate with dendritic cells to initiate Th2 responses, promote alternative activation of macrophages, and contribute to acquired resistance against parasites (12)(13)(14)(15)(16). We and others have shown that basophils contribute to protective immune responses against secondary infection by Nb and ticks (13,14,17). Antibodymediated depletion of basophils also was reported to result in partially impaired protection against Hp and Trichuris muris (18,19).…”

mentioning

confidence: 87%

Basophil-mediated protection against gastrointestinal helminths requires IgE-induced cytokine secretion

Schwartz

Turqueti-Neves

Hartmann

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Significance Gastrointestinal worms (helminths) infect more than 2 billion people, and vaccines are not yet available. Helminths elicit a type 2 immune response characterized by high serum IgE levels and increased numbers of IL-4– or IL-13–secreting effector cells including Th2 cells, eosinophils, basophils, and type 2 innate lymphoid cells. We determined the mechanism by which basophils contribute to protection against secondary infections with gastrointestinal helminths. Here we demonstrate that basophils are recruited into the small intestine of infected mice and orchestrate the local type 2 immune response in this tissue. Basophil-mediated protection required the presence of IgE and the expression of activating Fc receptors and IL-4/IL-13 in basophils. These findings could help the development of new vaccination strategies against helminths.

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“…63 Similarly, female mice are resistant to T. muris infection in the absence of IL-4 (in contrast to their male counterparts) mostly because of a stronger propensity for IL-13 production. 66 Furthermore, with the exception of IL-4 in the skin, 67 IL-4 appears to be dispensable for N. brasiliensis expulsion. 61,68 The redundancy between IL-4 and IL-13 likely stems from their shared usage of the IL-4Ra subunit, [69][70][71] although interestingly, IL-4Ra deficiency in T cells has no impact on worm expulsion during either T. spiralis, 72 H. polygyrus, 73 or N. brasiliensis 61,62 infections, in contrast to total IL-4Ra ablation.…”

Section: Transmissionmentioning

confidence: 99%