Show simple item record

dc.contributor.authorFelix, Krysta M.*
dc.contributor.authorJaimez, Ivan A.*
dc.contributor.authorNguyen, Thuy-Vi V.*
dc.contributor.authorMa, Heqing*
dc.contributor.authorRaslan, Walid A.*
dc.contributor.authorKlinger, Christina N.*
dc.contributor.authorDoyle, Kristian P.*
dc.contributor.authorWu, Hsin-Jung J.*
dc.date.accessioned2018-05-16T18:12:24Z
dc.date.available2018-05-16T18:12:24Z
dc.date.issued2018-04-18
dc.identifier.citationFelix KM, Jaimez IA, Nguyen T-VV, Ma H, Raslan WA, Klinger CN, Doyle KP and Wu H-JJ (2018) Gut Microbiota Contributes to Resistance Against Pneumococcal Pneumonia in Immunodeficient Rag−/− Mice. Front. Cell. Infect. Microbiol. 8:118. doi: 10.3389/fcimb.2018.00118en_US
dc.identifier.issn2235-2988
dc.identifier.doi10.3389/fcimb.2018.00118
dc.identifier.urihttp://hdl.handle.net/10150/627653
dc.description.abstractStreptococcus pneumoniae causes infection-related mortality worldwide. lmmunocompromised individuals, including young children, the elderly, and those with immunodeficiency, are especially vulnerable, yet little is known regarding S. pneumoniae-related pathogenesis and protection in immunocompromised hosts. Recently, strong interest has emerged in the gut microbiota's impact on lung diseases, or the "gut-lung axis." However, the mechanisms of gut microbiota protection against gut-distal lung diseases like pneumonia remain unclear. We investigated the role of the gut commensal, segmented filamentous bacteria (SFB), against pneumococcal pneumonia in immunocompetent and immunocompromised mouse models. For the latter, we chose the Rag(-/-) model, with adaptive immune deficiency. lmmunocompetent adaptive protection against S. pneumoniae infection is based on antibodies against pneumococcal capsular polysaccharides, prototypical T cell independent-II (TI-II) antigens. Although SFB colonization enhanced TI-II antibodies in C57BL/6 mice, our data suggest that SFB did not further protect these immunocompetent animals. Indeed, basal B cell activity in hosts without SFB is sufficient for essential protection against S. pneumoniae. However, in immunocompromised Rag(-/-) mice, we demonstrate a gut-lung axis of communication, as SFB influenced lung protection by regulating innate immunity. Neutrophil resolution is crucial to recovery, since an unchecked neutrophil response causes severe tissue damage. We found no early neutrophil recruitment differences between hosts with or without SFB; however, we observed a significant drop in lung neutrophils in the resolution phase of S. pneumoniae infection, which corresponded with lower CD47 expression, a molecule that inhibits phagocytosis of apoptotic cells, in SFB-colonized Rag(-/-) mice. SFB promoted a shift in lung neutrophil phenotype from inflammatory neutrophils expressing high levels of CD18 and low levels of CD62L, to pro-resolution neutrophils with low CD18 and high CD62L. Blocking CD47 in SFB(-) mice increased pro-resolution neutrophils, suggesting CD47 down-regulation may be one neutrophil-modulating mechanism SFB utilizes. The SFB-induced lung neutrophil phenotype remained similar with heat-inactivated S. pneumoniae treatment, indicating these SFB-induced changes in neutrophil phenotype during the resolution phase are not simply secondary to better bacterial clearance in SFB(+) than SFB(-) mice. Together, these data demonstrate that the gut commensal SFB may provide much-needed protection in immunocompromised hosts in part by promoting neutrophil resolution post lung infection.en_US
dc.description.sponsorshipNIH [R01AI107117]; Southwest Clinic and Research Institute Funden_US
dc.language.isoenen_US
dc.publisherFRONTIERS MEDIA SAen_US
dc.relation.urlhttps://www.frontiersin.org/articles/10.3389/fcimb.2018.00118/fullen_US
dc.rights© 2018 Felix, Jaimez, Nguyen, Ma, Raslan, Klinger, Doyle and Wu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).en_US
dc.subjectmicrobiotaen_US
dc.subjectStreptococcus pneumoniaeen_US
dc.subjectimmunocompromiseden_US
dc.subjectgut-lung axisen_US
dc.subjectsegmented filamentous bacteria (SFB)en_US
dc.subjectneutrophilsen_US
dc.subjectCD47en_US
dc.titleGut Microbiota Contributes to Resistance Against Pneumococcal Pneumonia in Immunodeficient Rag(-/-) Miceen_US
dc.typeArticleen_US
dc.contributor.departmentUniv Arizona, Dept Immunobiol, Tucson, AZ 85721 USAen_US
dc.contributor.departmentUniv Arizona, Coll Med, Dept Neurol, Tucson, AZ USAen_US
dc.contributor.departmentUniv Arizona, Coll Med, Arizona Arthrit Ctr, Tucson, AZ 85721 USAen_US
dc.identifier.journalFRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGYen_US
dc.description.noteOpen access journal.en_US
dc.description.collectioninformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.en_US
dc.eprint.versionFinal published versionen_US
refterms.dateFOA2018-05-16T18:12:25Z


Files in this item

Thumbnail
Name:
fcimb-08-00118.pdf
Size:
2.999Mb
Format:
PDF
Description:
Final Published Version

This item appears in the following Collection(s)

Show simple item record