Leukotriene B-4 licenses inflammasome activation to enhance skin host defense

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Guerta Salina, Ana Carolina ^{[1, 2, 3]} ; Brandt, Stephanie L. ^{[4, 2]} ; Klopfenstein, Nathan ^{[2, 5]} ; Blackman, Amondrea ^[2] ; Ribeiro Bazzano, Julia Miranda ^[2] ; Sa-Nunes, Anderson ^{[6, 2]} ; Byers-Glosson, Nicole ^[4] ; Brodskyn, Claudia ^[7] ; Tavares, Natalia Machado ^[7] ; Santos Da Silva, Icaro Bonyek ^[7] ; Medeiros, I, Alexandra ; Henrique Serezani, C. ^{[2, 5, 8, 9]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Biochem & Immunol, BR-14049900 Ribeirao Preto, SP - Brazil

^[2] Vanderbilt Univ, Dept Med, Div Infect Dis, Med Ctr, Nashville, TN 37232 - USA

^[3] I, Sao Paulo State Univ UNESP, Sch Pharmaceut Sci, Dept Biol Sci, BR-14800903 Araraquara, SP - Brazil

^[4] Indiana Univ Sch Med, Dept Microbiol & Immunol, Indianapolis, IN 46202 - USA

^[5] Vanderbilt Univ, Med Ctr, Vanderbilt Inst Infect Immunol & Inflammat, Nashville, TN 37232 - USA

^[6] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, BR-05508000 Sao Paulo, SP - Brazil

^[7] Fiocruz MS, Goncalo Moniz Inst, Oswaldo Cruz Fdn, BR-40296710 Salvador, BA - Brazil

^[8] Vanderbilt Univ, Med Ctr, Dept Pathol Microbiol & Immunol, Nashville, TN 37232 - USA

^[9] Vanderbilt Univ, Med Ctr, Vanderbilt Ctr Immunobiol, Nashville, TN 37232 - USA

• Tipo de documento: Artigo Científico
• Fonte: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA; v. 117, n. 48, p. 30619-30627, DEC 1 2020.
• Citações Web of Science: 0

Resumo

The initial production of inflammatory mediators dictates host defense as well as tissue injury. Inflammasome activation is a constituent of the inflammatory response by recognizing pathogen and host-derived products and eliciting the production of IL-1 beta and IL-18 in addition to inducing a type of inflammatory cell death termed ``pyroptosis.{''} Leukotriene B-4 (LTB4) is a lipid mediator produced quickly (seconds to minutes) by phagocytes and induces chemotaxis, increases cytokine/chemokine production, and enhances antimicrobial effector functions. Whether LTB4 directly activates the inflammasome remains to be determined. Our data show that endogenously produced LTB4 is required for the expression of pro-IL-1 beta and enhances inflammasome assembly in vivo and in vitro. Furthermore, LTB4-mediated Bruton's tyrosine kinase (BTK) activation is required for inflammasome assembly in vivo as well for IL-1 beta-enhanced skin host defense. Together, these data unveil a new role for LTB4 in enhancing the expression and assembly of inflammasome components and suggest that while blocking LTB4 actions could be a promising therapeutic strategy to prevent inflammasome-mediated diseases, exogenous LTB4 can be used as an adjuvant to boost inflammasome-dependent host defense. (AU)

• Processo FAPESP: 17/19870-6 - Efeito da fagocitose de células apoptóticas infectadas na ativação de macrófagos M1/M2
• Beneficiário: Alexandra Ivo de Medeiros
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 17/04786-0 - Ativação de Macrófagos M1/M2 pela eferocitose de células apoptóticas infectadas
• Beneficiário: Ana Carolina Guerta Salina
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 19/10839-4 - Decifrando as interações Aedes aegypti-hospedeiro vertebrado ao nível da pele usando imageamento por espectrometria de massas
• Beneficiário: Anderson de Sá Nunes
• Modalidade de apoio: Bolsas no Exterior - Pesquisa
• Processo FAPESP: 18/01622-9 - Ação de LTB4 na remoção de células apoptóticas infectadas durante infecção de pele por Staphylococcus aureus em camundongos diabéticos.
• Beneficiário: Ana Carolina Guerta Salina
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado