The role of IL-10 in immune responses against Pseudomonas aeruginosa during acute lung infection
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The role of IL‑10 in immune responses against Pseudomonas aeruginosa during acute lung infection Valéria Aparecida Belo1 · Jéssica Assis Pereira1 · Sara Franchin D. Souza1 · Fernanda de Lima Tana1 · Bruna P. Pereira2 · Débora de Oliveira Lopes3 · Carla S. Ceron2 · Rômulo D. Novaes4 · Patrícia Paiva Corsetti5 · Leonardo Augusto de Almeida1 Received: 23 April 2020 / Accepted: 22 September 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Pseudomonas aeruginosa is considered an opportunistic pathogen of great clinical importance. The clearance of this bacterium occurs through recognition of the pathogen by innate immune system receptors, leading to a lung inflammatory response. However, this response must be controlled via immunoregulatory pathways. In this study, we evaluate the role of endogenous murine IL-10 after acute infection with the virulent strain P. aeruginosa PA14. To assess the role of IL-10, intratracheal infection with the PA14 strain was performed in C57BL/6 or IL-10 KO mice. The PA14 strain was recovered in both types of animals, although IL-10 KO mice presented a higher number of viable bacteria in the lung when compared to the C57BL/6 group. Histopathological and stereological analyses showed that IL-10 KO mice had higher tissue damage and inflammatory infiltrate when compared to control animals. The activity of MMP-9 but not MMP-2, as well as IL-6 and TNF-α expression, were augmented in the lungs of infected animals and was much more evident in IL-10 KO animals when compared to the other analyzed groups. This work indicates that endogenous IL-10 control P. aeruginosa infection, the expression of pro-inflammatory genes, MMP-9 activity and histopathological processes of the infectious process in question. Keywords Interleukin-10 · P. aeruginosa · Lung infection · MMP-9 · Inflammatory response · Immunoregulation
Introduction Pseudomonas aeruginosa is an opportunistic pathogen that affects immunocompromised patients. Due to a variety of mechanisms of adaptation and resistance to multiple classes of antibiotics, infections by strains of P. aeruginosa * Leonardo Augusto de Almeida leonardo.almeida@unifal‑mg.edu.br; [email protected] 1
Departmento de Microbiologia E Imunologia, Universidade Federal de Alfenas, Alfenas, Brazil
2
Faculdade de Ciências Farmacêuticas, Universidade Federal de Alfenas, Alfenas, Brazil
3
Laboratório de Biologia Molecular, Universidade Federal de São João Del-Rei (CCO), Divinópolis, Brazil
4
Departamento de Biologia Estrutural, Universidade Federal de Alfenas, Alfenas, Brazil
5
Laboratório de Imunologia das Doenças Infecciosas E Crônicas, Universidade José Do Rosário Vellano, Alfenas, Minas Gerais, Brazil
can cause morbidity and mortality and represent a threat to public health (Moradali et al. 2017). To trigger an effective response against infection by P. aeruginosa, several pathogen-associated molecular patterns are recognized by innate immune receptors linked to specific acquired immunity. The innate im
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