Recruited inflammatory monocytes stimulate antiviral Th1 immunity in infected tissue

Iijima, Norifumi; Mattei, Lisa M.; Iwasaki, Akiko

doi:10.1073/pnas.1005201108

Cited by 164 publications

(178 citation statements)

References 43 publications

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“…However, no mechanism has been demonstrated. Given that tissue macrophages typically derive from circulating monocytes, and under conditions of tissue injury there is increased monocyte trafficking into diseased tissues (26,27), our results demonstrating decreased circulating monocyte levels upon FTY720 administration provide an explanation for these findings.…”

Section: Discussionmentioning

confidence: 57%

Circulating Monocytes Are Reduced by Sphingosine-1-Phosphate Receptor Modulators Independently of S1P3

Lewis

Haxhinasto

Anderson

et al. 2013

The Journal of Immunology

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Sphingosine-1-phosphate (S1P) receptors are critical for lymphocyte egress from secondary lymphoid organs, and S1P receptor modulators suppress lymphocyte circulation. However, the role of S1P receptors on monocytes is less clear. To elucidate this, we systematically evaluated monocytes in rats and mice, both in naive and inflammatory conditions, with S1P receptor modulators FTY720 and BAF312. We demonstrate that S1P receptor modulators reduce circulating monocytes in a similar time course as lymphocytes. Furthermore, total monocyte numbers were increased in the spleen and bone marrow, suggesting that S1P receptor modulation restricts egress from hematopoietic organs. Monocytes treated ex vivo with FTY720 had reduced CD40 expression and TNF-α production, suggesting a direct effect on monocyte activation. Similar reductions in protein expression and cytokine production were also found in vivo. Suppression of experimental autoimmune encephalomyelitis in mice and rats by FTY720 correlated with reduced numbers of lymphocytes and monocytes. These effects on monocytes were independent of S1P3, as treatment with BAF312, a S1P1,4,5 modulator, led to similar results. These data reveal a novel role for S1P receptors on monocytes and offer additional insights on the mechanism of action of S1P receptor modulators in disease.

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Section: Discussionmentioning

confidence: 57%

Circulating Monocytes Are Reduced by Sphingosine-1-Phosphate Receptor Modulators Independently of S1P3

Lewis

Haxhinasto

Anderson

et al. 2013

The Journal of Immunology

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“…CCR2 is a chemokine receptor required for the infiltration of Ly6C + monocytes into inflamed tissues in response to the chemotactic cytokine CCL2, and CCR2 −/− mice have been used extensively to study the role of inflammatory monocytes and Mø in various injury and disease models (e.g., refs. [32][33][34]. This mouse line has also been used to study neuropathic pain, which it reduced, and CFA-induced inflammatory pain, in which it had no effect (35), but has not been used to examine the pain response after incisional wound.…”

Section: Resultsmentioning

confidence: 99%

CD11b⁺Ly6G⁻myeloid cells mediate mechanical inflammatory pain hypersensitivity

Ghasemlou

Chiu

Julien

et al. 2015

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

156

135

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Pain hypersensitivity at the site of inflammation as a result of chronic immune diseases, pathogenic infection, and tissue injury is a common medical condition. However, the specific contributions of the innate and adaptive immune system to the generation of pain during inflammation have not been systematically elucidated. We therefore set out to characterize the cellular and molecular immune response in two widely used preclinical models of inflammatory pain: (i) intraplantar injection of complete Freund's adjuvant (CFA) as a model of adjuvant-and pathogen-based inflammation and (ii) a plantar incisional wound as a model of tissue injury-based inflammation. Our findings reveal differences in temporal patterns of immune cell recruitment and activation states, cytokine production, and pain in these two models, with CFA causing a nonresolving granulomatous inflammatory response whereas tissue incision induced resolving immune and pain responses. These findings highlight the significant differences and potential clinical relevance of the incisional wound model compared with the CFA model. By using various cell-depletion strategies, we find that, whereas lymphocyte antigen 6 complex locus G (Ly)6G + CD11b + neutrophils and T-cell receptor (TCR) β + T cells do not contribute to the development of thermal or mechanical pain hypersensitivity in either model, proliferating CD11b + Ly6G − myeloid cells were necessary for mechanical hypersensitivity during incisional pain, and, to a lesser extent, CFA-induced inflammation. However, inflammatory (CCR2 + Ly6C hi ) monocytes were not responsible for these effects. The finding that a population of proliferating CD11b + Ly6G − myeloid cells contribute to mechanical inflammatory pain provides a potential cellular target for its treatment in wound inflammation.pain | inflammation | cytokines | monocytes | macrophages

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“…Single-cell suspensions were prepared from the iliac lymph nodes and vagina according to previously described methods, with slight modifications (48). Single cells were pretreated with anti-CD16/32 antibody (2.4G2) to block Fc receptors, and then stained with the following antibodies: CD8α (53-6.7), B220 (RA3-6B2), Ly6C (AL-21), Ly6G (1A8), CD45.2 (104), CD11c (HL3), CD11b (M1/70), CD44 (IM7), Siglec-F (E50-2440), and NK 1.1 (PK136) (BD Biosciences); CD3e (145-2C11), CD4 (GK1.5), CD11c (N418), CD317 (BST-2, eBio927), CD62L (MEL-14), FceRI (MAR-1), Sca-1 (D7), c-kit (2B8), and IL-7R (CD127, A7R34) (eBioscience); MHCII (M5/114.15.2), and ST2 (DIH9) (BioLegend).…”

Section: Methodsmentioning

confidence: 99%

Dysbiosis-induced IL-33 contributes to impaired antiviral immunity in the genital mucosa

Kim

Chang

et al. 2016

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

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Commensal microbiota are well known to play an important role in antiviral immunity by providing immune inductive signals; however, the consequence of dysbiosis on antiviral immunity remains unclear. We demonstrate that dysbiosis caused by oral antibiotic treatment directly impairs antiviral immunity following viral infection of the vaginal mucosa. Antibiotic-treated mice succumbed to mucosal herpes simplex virus type 2 infection more rapidly than water-fed mice, and also showed delayed viral clearance at the site of infection. However, innate immune responses, including type I IFN and proinflammatory cytokine production at infection sites, as well as induction of virusspecific CD4 and CD8 T-cell responses in draining lymph nodes, were not impaired in antibiotic-treated mice. By screening the factors controlling antiviral immunity, we found that IL-33, an alarmin released in response to tissue damage, was secreted from vaginal epithelium after the depletion of commensal microbiota. This cytokine suppresses local antiviral immunity by blocking the migration of effector T cells to the vaginal tissue, thereby inhibiting the production of IFN-γ, a critical cytokine for antiviral defense, at local infection sites. These findings provide insight into the mechanisms of homeostasis maintained by commensal bacteria, and reveal a deleterious consequence of dysbiosis in antiviral immune defense.commensal microbiota | dysbiosis | IL-33 | herpes simplex virus type 2 | genital tract

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Recruited inflammatory monocytes stimulate antiviral Th1 immunity in infected tissue

Cited by 164 publications

References 43 publications

Circulating Monocytes Are Reduced by Sphingosine-1-Phosphate Receptor Modulators Independently of S1P3

Circulating Monocytes Are Reduced by Sphingosine-1-Phosphate Receptor Modulators Independently of S1P3

CD11b⁺Ly6G⁻myeloid cells mediate mechanical inflammatory pain hypersensitivity

Dysbiosis-induced IL-33 contributes to impaired antiviral immunity in the genital mucosa

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Recruited inflammatory monocytes stimulate antiviral Th1 immunity in infected tissue

Cited by 164 publications

References 43 publications

Circulating Monocytes Are Reduced by Sphingosine-1-Phosphate Receptor Modulators Independently of S1P3

Circulating Monocytes Are Reduced by Sphingosine-1-Phosphate Receptor Modulators Independently of S1P3

CD11b+Ly6G−myeloid cells mediate mechanical inflammatory pain hypersensitivity

Dysbiosis-induced IL-33 contributes to impaired antiviral immunity in the genital mucosa

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CD11b⁺Ly6G⁻myeloid cells mediate mechanical inflammatory pain hypersensitivity