Variation in inflammatory response during pneumococcal infection is influenced by host-pathogen interactions but associated with animal srvival

Jonczyk, Magda S., Escudero, Laura, Sylvius, Nicolas, Norman, Martin, Henriques-Normark, Birgitta, Andrew, Peter W. and Pirofski, L. 2016. Variation in inflammatory response during pneumococcal infection is influenced by host-pathogen interactions but associated with animal srvival. Infection and Immunity 84 (4) , pp. 894-905. 10.1128/IAI.01057-15

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Abstract

Inflammation is a crucial part of innate immune responses but, if imbalanced, can lead to serious clinical conditions or even death. Cytokines regulate inflammation, and studies report their impact on clinical outcome. However, host and pathogen genetic backgrounds influence cytokine production, making it difficult to evaluate which inflammatory profiles (if any) relate to improved prognosis. Streptococcus pneumoniae is a common human pathogen associated with asymptomatic nasopharyngeal carriage. Infrequently, it can lead to a wide range of diseases with high morbidity and mortality rates. Studies show that both pneumococcal serotype and host genetic background affect the development of disease and contribute to variation in inflammatory responses. In this study, we investigated the impact of the host and pneumococcal genetic backgrounds on pulmonary cytokine responses and their relationship to animal survival. Two inbred mouse strains, BALB/c and CBA/Ca, were infected with 10 pneumococcal strains, and the concentrations of six pulmonary cytokines were measured at 6 h and 24 h postinfection. Collected data were analyzed by principal-component analysis to identify whether there is any pattern in the observed cytokine variation. Our results show that host-pneumococcus combination was at the core of observed variation in cytokine responses, yet the resulting cytokine profile discriminated only between survivors and fatalities but not mouse or pneumococcal strains used during infection. Therefore, our results indicate that although alternative inflammatory profiles are generated during pneumococcal infection, a common pattern emerged, which determined the clinical outcome of pneumococcal infections.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Publisher:	American Society for Microbiology
ISSN:	0019-9567
Date of First Compliant Deposit:	22 August 2017
Date of Acceptance:	23 December 2015
Last Modified:	05 May 2023 10:54
URI:	https://orca.cardiff.ac.uk/id/eprint/103813

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