Defective B-1 Cell Development and Impaired Immunity against Angiostrongylus cantonensis in IL-5Rα-Deficient Mice

Yoshida, Toshimi; Ikuta, Koichi; Sugaya, Hiroko; Maki, Kazushige; Takagi, Mineo; Kanazawa, Hiroko; Sunaga, Shinji; Kinashi, Tatsuo; Yoshimura, Kentarou; Miyazaki, Jun‐ichi; Takaki, Satoshi; Takatsu, Kiyoshi

doi:10.1016/s1074-7613(00)80414-8

Cited by 211 publications

(141 citation statements)

References 78 publications

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“…Although different ways of inoculating tumor cells were employed, innate IL-5-producing non-T cells might also contribute to such early eosinophil regulation because IL-5 was upregulated immediately after tumor inoculation. The reduction of eosinophils in the IL-5 or IL-5Ra KO mice tends to be more severe in the lung than in the bone marrow and the blood in steady-state, naive animals (11,12). Together with our finding that innate IL-5-producing cells were most abundant in the lung, it seems likely that lung eosinophil largely depends on IL-5.…”

Section: Discussionsupporting

confidence: 48%

“…1E). B-1 B cells in IL-5 V/V mice were smaller in size, as observed in IL-5Ra knockout (KO) mice (11) (Fig. 1F).…”

Section: Generation Of Il-5/venus Ki Micementioning

confidence: 61%

“…IL-5 binds the IL-5R complex, which consists of an IL-5Ra chain specific for IL-5 and a common b-chain that is shared by the receptors for IL-3 and GM-CSF. IL-5 signaling is also necessary for the maintenance of B-1 B cells in the peritoneal and pleural cavities (11,12) and has been implicated to play a critical role in mucosal immunity, such as IgA production. IL-5 transgenic mice exhibited expansion of B-1 B cells and elevated levels of serum IgA in addition to massive eosinophilia in various tissues (13).…”

mentioning

confidence: 99%

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Identification of Innate IL-5–Producing Cells and Their Role in Lung Eosinophil Regulation and Antitumor Immunity

Ikutani

Yanagibashi

Ogasawara

et al. 2012

The Journal of Immunology

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273

208

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IL-5 is involved in a number of immune responses such as helminth infection and allergy. IL-5 also plays roles in innate immunity by maintaining B-1 B cells and mucosal IgA production. However, the identity of IL-5–producing cells has not been unambiguously characterized. In this report, we describe the generation of an IL-5 reporter mouse and identify IL-5–producing non-T lymphoid cells that reside in the intestine, peritoneal cavity, and lungs in naive mice. They share many characteristics with natural helper cells, nuocytes, and Ih2 cells, including surface Ags and responsiveness to cytokines. However, these phenotypes do not completely overlap with any particular one of these cell types. Innate non-T IL-5–producing cells localized most abundantly in the lung and proliferated and upregulated IL-5 production in response to IL-25 and IL-33. IL-33 was more effective than IL-25. These cells contribute to maintaining sufficient numbers of lung eosinophils and are important for eosinophil recruitment mediated by IL-25 and IL-33. Given that eosinophils are shown to possess antitumor activity, we studied lung tumor metastasis and showed that innate IL-5–producing cells were increased in response to tumor invasion, and their regulation of eosinophils is critical to suppress tumor metastasis. Genetic blockade or neutralization of IL-5 impaired eosinophil recruitment into the lung and resulted in increased tumor metastasis. Conversely, exogenous IL-5 treatment resulted in suppressed tumor metastasis and augmented eosinophil infiltration. These newly identified innate IL-5–producing cells thus play a role in tumor surveillance through lung eosinophils and may contribute to development of novel immunotherapies for cancer.

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Section: Discussionsupporting

confidence: 48%

“…1E). B-1 B cells in IL-5 V/V mice were smaller in size, as observed in IL-5Ra knockout (KO) mice (11) (Fig. 1F).…”

Section: Generation Of Il-5/venus Ki Micementioning

confidence: 61%

mentioning

confidence: 99%

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Identification of Innate IL-5–Producing Cells and Their Role in Lung Eosinophil Regulation and Antitumor Immunity

Ikutani

Yanagibashi

Ogasawara

et al. 2012

The Journal of Immunology

Self Cite

273

208

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“…Accordingly, IL-5 transgenic mice have (in addition to eosinophilia) increased numbers of B-1 cells in the peritoneal cavity and elevated levels of serum IgM and IgA (46), while IL-5Rα -/-mice do not show IL-5-induced enhancement of B cell responses to TI type 2 (TI-2) antigens (47). Immune responses to PC are examples of classic TI-2 responses.…”

Section: Discussionmentioning

confidence: 99%

IL-5 links adaptive and natural immunity specific for epitopes of oxidized LDL and protects from atherosclerosis

Binder

Hartvigsen²,

Chang³

et al. 2004

J. Clin. Invest.

255

241

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“…Increased susceptibility to intracranial dissemination of Angiostrongylus cantonensis in IL-5␣-deficient mice has been reported, reinforcing the importance of IL-5 in the induction of eosinophilassociated killing of invasive helminths. 20 In addition to direct damage produced by the migrating larvae and their products, it is likely that eosinophil-derived neurotoxin contributes to the neurologic manifestations of B procyonis encephalitis. The link between eosinophils and neurotoxicity was first described by M. H. Gordon in 1933.…”

Section: Discussionmentioning

confidence: 99%

Eosinophil-Associated Inflammation and Elaboration of Eosinophil-Derived Proteins in 2 Children With Raccoon Roundworm (Baylisascaris procyonis)Encephalitis

Moertel

Kazacos

Butterfield³

et al. 2001

Pediatrics

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ABSTRACT. Objective. Eosinophil-associated proteins, especially eosinophil-derived neurotoxin, may be important contributors to the neurologic pathology and symptoms caused by Baylisascaris procyonis infection.Methods. Two cases of severe B procyonis encephalitis with evidence of marked eosinophil degranulation in the central nervous system are presented. Serial cerebrospinal fluid (CSF) specimens were collected from each patient during the course of their illness. Antibodies against B procyonis were measured in the patients' serum and CSF. Levels of the eosinophilopoietin interleukin-5 (IL-5) and 2 important eosinophil proteins, eosinophilderived neurotoxin and major basic protein, were assayed in the CSF.Results. Both patients had rapidly progressive central nervous system disease with evidence of eosinophilic meningoencephalitis. Both tested positive for antibodies to B procyonis in serum and CSF and had progressively worsening deep white matter changes on magnetic resonance images of the brain. CSF levels of IL-5, eosinophilderived neurotoxin, and major basic protein were markedly elevated over controls.Conclusions. This is the first report of the measurement of IL-5, eosinophil-derived neurotoxin, and major basic protein in human CSF. In addition to traumatic damage and necrosis caused by migrating larvae, eosinophil-derived neurotoxin from associated eosinophilic inflammation may be an important contributory factor in the pathogenesis of B procyonis encephalitis. Pediatrics 2001;108(5). URL: http://www.pediatrics.org/cgi/content/ full/108/5/e93; parasite, eosinophil-derived-neurotoxin, major basic protein, eosinophilia, hypereosinophilia, interleukin-5, encephalitis, child.ABBREVIATIONS. CSF, cerebrospinal fluid; CNS, central nervous system; MRI, magnetic resonance imaging; IL-5, interleukin-5; PBS, phosphate-buffered saline.B aylisascaris procyonis, the common raccoon ascarid, is a well-known cause of severe neurologic disease (neural larva migrans) in animals, with cases identified in Ͼ90 species of mammals and birds in North America. 1,2 Neural larva migrans and eosinophilic meningoencephalitis attributable to B procyonis have now been identified in 7 young children, including the 2 reported here. [3][4][5][6][7] We specifically note a novel correlation with elevated cerebrospinal fluid (CSF) levels of major basic protein and the neurotoxic protein eosinophil-derived neurotoxin associated with eosinophilic inflammation in these 2 cases. We hypothesize that the severe neurologic consequences of Baylisascaris encephalitis are attributable, in part, to marked eosinophil degranulation and release of these toxic eosinophil proteins in the central nervous system (CNS) of patients with this disease. CASE REPORTS Case 1A 13-month-old boy became irritable 3 weeks before hospital admission, then became progressively irritable, ataxic, and weak. Three days before admission, he was unable to cruise, sit up, or walk, and exhibited dysmetria. He then had an episode of limb twitching followed by rigidity and decreased...

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Defective B-1 Cell Development and Impaired Immunity against Angiostrongylus cantonensis in IL-5Rα-Deficient Mice

Cited by 211 publications

References 78 publications

Identification of Innate IL-5–Producing Cells and Their Role in Lung Eosinophil Regulation and Antitumor Immunity

Identification of Innate IL-5–Producing Cells and Their Role in Lung Eosinophil Regulation and Antitumor Immunity

IL-5 links adaptive and natural immunity specific for epitopes of oxidized LDL and protects from atherosclerosis

Eosinophil-Associated Inflammation and Elaboration of Eosinophil-Derived Proteins in 2 Children With Raccoon Roundworm (Baylisascaris procyonis)Encephalitis

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