IL-33 Shifts Macrophage Polarization, Promoting Resistance against<i>Pseudomonas aeruginosa</i>Keratitis

Hazlett, Linda D.; McClellan, Sharon A.; Barrett, Ronald P.; Huang, Xi; Zhang, Yunfan; Wu, Minhao; Rooijen, Nico van; Szliter, Elizabeth A.

doi:10.1167/iovs.09-3983

Cited by 91 publications

(70 citation statements)

References 38 publications

(49 reference statements)

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“…In Pneumocystis murina lung infection, IL-33 enhances the killing activity of macrophages (33). An IL-33-mediated reduction of Pseudomonas aeruginosa-induced corneal keratitis correlates with M2 macrophage polarization and the decrease in bacterial numbers in the cornea (34). In our model, IL-33-sensitized peritoneal macrophages displayed a significantly lower phagocytic activity against C. albicans (Fig.…”

Section: Discussionmentioning

confidence: 58%

IL-33–Induced Hematopoietic Stem and Progenitor Cell Mobilization Depends upon CCR2

Kim

et al. 2014

The Journal of Immunology

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IL-33 has been implicated in the pathogenesis of asthma, atopic allergy, anaphylaxis, and other inflammatory diseases by promoting the production of proinflammatory cytokines and chemokines or Th2 immune responses. In this study, we analyzed the in vivo effect of IL-33 administration. IL-33 markedly promoted myelopoiesis in the bone marrow and myeloid cell emigration. Concomitantly, IL-33 induced hematopoietic stem and progenitor cell (HSPC) mobilization and extramedullary hematopoiesis. HSPC mobilization was mediated mainly through increased levels of CCL7 produced by vascular endothelial cells in response to IL-33. In vivo treatment of IL-33 rapidly induced phosphorylation of ERK, JNK, and p38, and inhibition of these signaling molecules completely blocked the production of CCL7 induced by IL-33. Consistently, inhibitor of CCR2 markedly reduced IL-33–mediated HSPC mobilization in vivo and migration of HSPCs in response to CCL7 in vitro. IL-33–mobilized HSPCs were capable of homing to, and of long-term reconstitution in, the bone marrow of irradiated recipients. Immune cells derived from these recipients had normal antifungal activity. The ability of IL-33 to promote migration of HSPCs and myeloid cells into the periphery and to regulate their antifungal activity represents a previously unrecognized role of IL-33 in innate immunity. These properties of IL-33 have clinical implications in hematopoietic stem cell transplantation.

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Section: Discussionmentioning

confidence: 58%

IL-33–Induced Hematopoietic Stem and Progenitor Cell Mobilization Depends upon CCR2

Kim

et al. 2014

The Journal of Immunology

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“…IL-33 and ST2 are both expressed in the normal cornea in resistant BALB/c mice and susceptible C57BL/6 mice. In a model of corneal infection, the IL-33/ST2 expression levels were significantly higher in infected BALB/c mice than in C57BL/6 mice and decreased after 5 days (17,53). In BALB/c mice, the use of a blocking fusion protein, ST2-Fc, led to impaired control of the bacterial load, improved neutrophil influx, increased levels of proinflammatory and Th1 cytokines in the cornea, and decreased levels of Th2 cytokines (53).…”

Section: The Il-33/st2 Axis and Bacterial Infectionsmentioning

confidence: 98%

“…IL-33 is mainly associated with the initiation or progression of specific Th2 responses through secretion of IL-5 and IL-13. IL-33 contributes to macrophage alternative polarization, dendritic cell regulation, and direct effects on T cells (1,(17)(18)(19)(20). These pleiotropic effects explain how IL-33 plays contrasting roles in human diseases.…”

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confidence: 99%

Crucial and Diverse Role of the Interleukin-33/ST2 Axis in Infectious Diseases

et al. 2015

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“…IL-33 acts on a variety of cells of the innate arm of immunity, including neutrophils, macrophages, dendritic cells, mast cells, basophils, and eosinophils, and functions as an amplifier of inflammation (5)(6)(7)(8)(9)(10)(11)(12)(13). Recent studies have suggested that IL-33 plays a role in infection-related inflammation, as IL-33 is protective against infection by opportunistic pathogens such as Pseudomonas aeruginosa, Pneumocystis murina, Cryptococcus neoformans, and polymicrobes (6,8,9,14). Prior to this study, there had been no publications regarding the role of IL-33 in Candida albicans infections.…”

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confidence: 99%

IL-33 Priming Regulates Multiple Steps of the Neutrophil-Mediated Anti-Candida albicans Response by Modulating TLR and Dectin-1 Signals

Tran

Kim

et al. 2012

The Journal of Immunology

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IL-33 is known to play an important role in Th2 immunity. In this study, we investigated the effect of IL-33 pretreatment on anti-fungal response using an acute Candida albicans peritoneal infection model. IL-33 pretreatment induced a rapid fungal clearance and markedly reduced the C. albicans infection-associated mortality. The priming effect of IL-33 occurred during multiple steps of the neutrophil-mediated anti-fungal response. First, the anti-fungal effect occurred due to the rapid and massive recruitment of neutrophils to the site of infection as a result of the release of CXCR2 chemokines by peritoneal macrophages and by reversal of the TLR-induced reduction of CXCR2 expression in neutrophils during IL-33 priming. Second, conditioning of neutrophils by IL-33 activated the TLR and dectin-1 signaling pathways, leading to the upregulation of complement receptor 3 expression induced by C. albicans. Upregulated CR3 in turn increased the phagocytosis of opsonized C. albicans and resulted in the production of high levels of reactive oxygen species and the subsequent enhanced killing activity of neutrophils. Taken together, our results suggest that IL-33 can regulate the anti-fungal activity of neutrophils by collaborative modulation of the signaling pathways of different classes of innate immune receptors.

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IL-33 Shifts Macrophage Polarization, Promoting Resistance againstPseudomonas aeruginosaKeratitis

Abstract: These data provide evidence that IL-33 promotes a Th2-type immune response and reduces inflammation by polarizing the Mvarphi production of anti-inflammatory mediators in the cornea.

Cited by 91 publications

References 38 publications

IL-33–Induced Hematopoietic Stem and Progenitor Cell Mobilization Depends upon CCR2

IL-33–Induced Hematopoietic Stem and Progenitor Cell Mobilization Depends upon CCR2

Crucial and Diverse Role of the Interleukin-33/ST2 Axis in Infectious Diseases

IL-33 Priming Regulates Multiple Steps of the Neutrophil-Mediated Anti-Candida albicans Response by Modulating TLR and Dectin-1 Signals

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