Commensal-dendritic cell interactions specifies a unique protective skin immune signature.

Naik S*, Bouladoux N*, Linehan J, Han SJ, Harrison OJ, Wilhelm C, Conlan S, Himmelfarb S, Byrd A, Deming C, Quinones M, Brenchley JM, Kong H, Tussiwand R, Murphy KM, Merad M, Segre JA and Belkaid Y. Commensal-dendritic cell interactions specifies a unique protective skin immune signature. Nature. 520(7545): 104-108 April 2015.

Here we show that defined commensals dominantly affect skin immunity and identify the cellular mediators involved in this specification.This interaction may represent an evolutionary means by which the skin immune system uses fluctuating commensal signals to calibrate barrier immunity and provide heterologous protection against invasive pathogens. These findings reveal that the skin immune landscape is a highly dynamic environment that can be rapidly and specifically remodelled by encounters with defined commensals, findings that have profound implications for our understanding of tissue-specific immunity and pathologies.

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Commensal bacteria control cancer response to therapy by modulating the tumor microenvironment.

Iida N, Dzutsev A, Stewart A, Bouladoux N, Smith L, Salcedo R, Cardone M, Back T, Kiu H, Cramer S, Naik S, Patri A, Wang E, Marincola FM, Belkaid Y, Trinchieri G and Goldszmid RS. Commensal bacteria control cancer response to therapy by modulating the tumor microenvironment. Science. 342(6161):967-70. Nov, 2013

The gut microbiota influences both local and systemic inflammation. Inflammation contributes to development, progression, and treatment of cancer, but it remains unclear whether commensal bacteria affect inflammation in the sterile tumor microenvironment. Here, we show that disruption of the microbiota impairs the response of subcutaneous tumors to CpG-oligonucleotide immunotherapy and platinum chemotherapy.

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Intraluminal containment of commensal outgrowth in the gut during infection induced dysbiosis.

Molloy MJ*, Grainger JR*, Bouladoux N*, Hand TW, Naik S, Quimones M, Dzutsev AK, Gao JL, Trinchieri G, Murphy PM and Belkaid Y. Intraluminal containment of commensal outgrowth in the gut during infection induced dysbiosis. Cell Host Microbe. 14(3):318-28. Sept, 2013

Shifts in commensal microbiota composition are emerging as a hallmark of gastrointestinal inflammation. In particular, outgrowth of γ-proteobacteria has been linked to the etiology of inflammatory bowel disease and the pathologic consequences of infections. Here we show that following acute Toxoplasma gondiigastrointestinal infection of mice, control of commensal outgrowth is a highly coordinated process involving both the host response and microbial signals.

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Compartmentalized and systemic control of tissue immunity by commensals.

Belkaid Y and Naik S. Compartmentalized and systemic control of tissue immunity by commensals. Nature Immunology. 14(7):646-53 June, 2013

In this Perspective, we discuss how resident commensals outside the gastrointestinal tract can control unique physiological niches and the potential implications of the dialog between these commensals and the host for the establishment of immune homeostasis, protective responses and tissue pathology.

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Signaling via the IL-20 receptor inhibits cutaneous production of IL-1β and IL-17A to promote infection with methicillin-resistant Staphylococcus aureus.

Myles IA, Fontecilla N , Valdez PA, Vithayathil P, Naik S, Belkaid Y, Ouyang W and Datta SK. Signaling via the IL-20 receptor inhibits cutaneous production of IL-1b and IL-17A to promote infection with methicillin-resistant Staphylococcus aureus. Nature Immunology. 14(8):804-11 June, 2013

Staphylococcus aureus causes most infections of human skin and soft tissue and is a major infectious cause of mortality. Host defense mechanisms against S. aureus are incompletely understood. Interleukin 19 (IL-19), IL-20 and IL-24 signal through type I and type II IL-20 receptors and are associated with inflammatory skin diseases such as psoriasis and atopic dermatitis.  Our findings identify an immunosuppressive role for IL-19, IL-20 and IL-24 during infection that could be therapeutically targeted to alter susceptibility to infection.

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