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.
Similar content being viewed by others
References
Baddeley AJ, Gundersen HJ, Cruz-Orive LM (1986) Estimation of surface area from vertical sections. J Microsc 142:259–276
Chen W, Lian J, Ye J, Mo Q, Qin J, Hong G, Long-Wang C, Shao-Ce Z, Guang-Ju Z, Zhong-Qiu L (2017) Ethyl pyruvate reverses development of Pseudomonas aeruginosa pneumonia during sepsis-induced immunosuppression. Int Immunopharmacol 52:61–69
Chmiel JF, Konstan MW, Knesebeck JE, Hilliard TL, Dawson DV, Berger M (1999) IL-10 attenuates excessive inflammation in chronic pseudomonas infection in mice. Am J Respir Crit Care Med 160:2040–2047
Chmiel JF, Konstan MW, Saadane A, Krenicky JE, Kirchner HL, Berger M (2002) Prolonged inflammatory response to acute pseudomonas challenge in interleukin-10 knockout mice. Am J Respir Crit Care Med 165:1176–1181
Corsetti PP, De Almeida LA, Carvalho NB, Azevedo V, Silva T, Teixeira HC, Faria AC, Oliveira S (2013) Enhances production of proinflammatory cytokines and leads to Brucella abortus clearance in mice. PLoS ONE 9:0074729
Guilbault C, Stotland P, Lachance C, Tam M, Keller A, Thompson-Snipes L, Cowley E, Hamilton T, Eidelman DH, Stevenson MM, Radiozioch D (2002) Influence of gender and interleukin-10 deficiency on the inflammatory response during lung infection with Pseudomonas aeruginosa in mice. Immunology 107:297–305
Kothari P, Pestana R, Mesraoua R, Elchaki R, Khan KM, Dannenberg AJ, Falcone D (2014) IL-6-mediated induction of matrix metalloproteinase-9 is modulated by JAK-dependent IL-10 expression in macrophages. J Immunology 192:349–357
Leech JM, Lacey KA, Mulcahy ME, Medina E, Mcloughlin RM (2017) IL-10 plays opposing roles during Staphylococcus aureus systemic and localized infections. J Immunol 198:2352–2365
Li WL, Wu CH, Yang J, Tang M, Chen LJ, Zhao SL (2015) Local inflammation alters MMP-2 and MMP-9 gelatinase expression associated with theseverity of nifedipine-induced gingival overgrowth: a rat model study. Inflammation. 38(4):1517-28.
Li Y, Chen L, Wang C, Chen J, Zhang X, Hu Y, Niu X, Pei D, He Z, Bi Y (2016) Extracellular matrix metalloproteinase inducer enhances host resistanceagainst Pseudomonas aeruginosa infection through MAPK signaling pathway. Am J Transl Res 8(12):5619-5627.
Lovewell RR, Patankar YR, Berwin B (2014) Mechanisms of phagocytosis and host clearance of Pseudomonas aeruginosa. Am J Physiol Lung Cell MoL Physiol 306:591–603
Mandarim-de-Lacerda CA (2003) Stereological tools in biomedical research. An Acad Bras Cienc 75:469–486
Mitzner W, Fallica J, Bishai J (2008) Anisotropic nature of mouse lung parenchyma. Ann Biomed Eng 36:2111–2120
Moradali M, Ghods S, Rehm B (2017) Pseudomonas aeruginosa lifestyle: a paradigm for adaptation, survival, and persistence. Front Cell Infect Microbiol 7:39
Novaes RD, Gonçalves RV, Cupertino MC, Marques DCS, Rosa DD, Peluzio MCG, Neves CA, Leite JPV (2012) Bark extract of Bathysa cuspidata attenuates extra-pulmonary acute lung injury induced by paraquat and reduces mortality in rats. Int J Exp Pathol 93:225–233
Novaes RD, Penitente AR, Talvani A, Natali AJ, Neves CA, Maldonado IR (2012) Use of fluorescence in a modified disector method to estimate the number of myocytes in cardiac tissue. Arq Bras Cardiol 98:252–258
Parks WC, Wilson CL, López-Boado Y (2004) Matrix metalloproteinases as modulators of inflammation and innate immunity. Nat Rev Immunol 8:617–629
Peñaloza HF, Schultz BM, Nieto PA, Salazar GA, Suazo I, Gonzalez PA et al (2016) Opposing roles of IL-10 in acute bacterial infection. Cytokine Growth Factor Rev 32:17–30
Peñaloza HF, Noguera LP, Riedel CA, Bueno SM (2018) IL-10 plays opposing roles during Staphylococcus aureus systemic and localized infections. Frontiers in Microbiology 198:2352–2365
Rocha Pereira AE, Rodrigues MÂ, Novaes RD, Caldas IS, Martins Souza RL, Costa Pereira AA (2017) Lipopolysaccharide-induced acute lung injury in mice chronically infected by Schistosoma mansoni. Exp Parasitol 178:21–29
Rosa CP, Pereira JA, de Melo C, Santos N, Brancaglion GA, Silva EM, Tagliati CA, Novaes RD, Corsetti PP, de Almeida LA (2020) Vancomycin-induced gut dysbiosis during Pseudomonas aeruginosa pulmonary infection in a mice model. J Leukoc Biol 107(1):95–104
Weibel ER (1989) Measuring through the microscope: development and evolution of stereological methods. J Microsc 155:393–403
Weibel ER, Hsia CC, Ochs M (2007) How much is there really? Why stereology is essential in lung morphometry. J Appl Physiol 102:459–467
Wonnenberg B, Bischoff M, Beisswenger C, Dinh T, Bals R, Singh B, Tschering T (2016) The role of IL-1β in Pseudomonas aeruginosa in lung infection. Cell Tissue Res 364(2):225–229
Zhang R, Ni HJ, Zhou HS (2017) Study on the expression of Toll-like receptor 4 and matrix metalloproteinase-9 in patients with chronic obstructive pulmonary disease and their clinical significance. Eur Rev Medical Pharmacol Sci 21(9):2185–2191
Buff SM, Yu H, McCall JN, Caldwell SM, Ferkol TW, Flotte TR, Virella-Lowell IL (2010) IL-10 delivery by AAV5 vector attenuates inflammation in mice with Pseudomonas pneumonia. Gene Ther. 17(5):567‐576.
Christofi T, Apidianakis Y (2013) Drosophila immune priming against Pseudomonas aeruginosa short-lasting and depends on cellular and humoral immunity. F1000Research 1: 2–76
Raoust E, Balloy V, Garcia-Verdugo I, Touqui L, Ramphal R, Chignard, M (2009) Pseudomonas aeruginosa LPS or flagellin are sufficient to activate TLR-dependent signaling in murine alveolar macrophages and airway epithelial cells. PLoS ONE.
Funding
This study was supported in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES) (Finance Code 001).
Author information
Authors and Affiliations
Contributions
VAB, SFDS, FLT, DOL, CSC, RDN, PPC and LAA designed the project and experiments. VAB, JAP, SFDS, FLT and BPP carried out most of the experiments. VAB, JAP, RDN, PPC and LAA wrote the manuscript. VAB, SFDS, BPP and LAA carried out statistical analysis and prepared figures. LAA submitted this paper. All authors reviewed the manuscript.
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Ethical approval
This study was carried out in strict accordance with the Brazilian laws on animal experimentation. The protocol was approved by the Ethics Committee on the Use of Animals at the Federal University of Alfenas, Minas Gerais, Brazil (Permit Number: CEUA no. 42/2017). The experimentation was carried out in collaboration with the Laboratory of Molecular Biology at the Federal University of São João Del-Rei, Dona Lindu Center West Campus, Minas Gerais, Brazil, which had certification CQB 301/10
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Belo, V.A., Pereira, J.A., Souza, S.F.D. et al. The role of IL-10 in immune responses against Pseudomonas aeruginosa during acute lung infection. Cell Tissue Res 383, 1123–1133 (2021). https://doi.org/10.1007/s00441-020-03308-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00441-020-03308-4