title: Variation in Inflammatory Response during Pneumococcal Infection Is Influenced by Host-Pathogen Interactions but Associated with Animal Survival.
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 pneumonia 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.
authors.affiliation: Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, United Kingdom magdalena.jonczyk@nottingham.ac.uk pwa@leicester.ac.uk.
authors.forename: Magda S
authors.identifier: http://orcid.org/0000-0003-2117-1143
authors.initials: MS
authors.lastname: Jonczyk
authors.affiliation: Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, United Kingdom.
authors.forename: Laura
authors.initials: L
authors.lastname: Escudero
authors.affiliation: Department of Genetics, University of Leicester, Leicester, United Kingdom.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Sylvius
authors.affiliation: Department of Microbiology, Tumor and Cellbiology, Karolinska Institutet, Stockholm, Sweden, and Department of Clinical Microbiology, Karolinska University Hospital, Solna, Sweden.
authors.forename: Martin
authors.initials: M
authors.lastname: Norman
authors.affiliation: Department of Microbiology, Tumor and Cellbiology, Karolinska Institutet, Stockholm, Sweden, and Department of Clinical Microbiology, Karolinska University Hospital, Solna, Sweden.
authors.forename: Birgitta
authors.initials: B
authors.lastname: Henriques-Normark
authors.affiliation: Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, United Kingdom magdalena.jonczyk@nottingham.ac.uk pwa@leicester.ac.uk.
authors.forename: Peter W
authors.initials: PW
authors.lastname: Andrew
mesh_terms: D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D054884:Host-Pathogen Interactions / Q000235:genetics* / Q000502:physiology; D007249:Inflammation / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D020411:Oligonucleotide Array Sequence Analysis; D011008:Pneumococcal Infections / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D012313:RNA / Q000235:genetics / Q000378:metabolism; D013296:Streptococcus pneumoniae / Q000145:classification / Q000235:genetics
chemical_list: D016207:Cytokines; D012313:RNA