The B-cell inhibitory receptor CD22 is a major factor in host resistance to Streptococcus pneumoniae infection.


Journal

PLoS pathogens
ISSN: 1553-7374
Titre abrégé: PLoS Pathog
Pays: United States
ID NLM: 101238921

Informations de publication

Date de publication:
04 2020
Historique:
received: 05 07 2019
accepted: 06 03 2020
entrez: 24 4 2020
pubmed: 24 4 2020
medline: 5 8 2020
Statut: epublish

Résumé

Streptococcus pneumoniae is a major human pathogen, causing pneumonia and sepsis. Genetic components strongly influence host responses to pneumococcal infections, but the responsible loci are unknown. We have previously identified a locus on mouse chromosome 7 from a susceptible mouse strain, CBA/Ca, to be crucial for pneumococcal infection. Here we identify a responsible gene, Cd22, which carries a point mutation in the CBA/Ca strain, leading to loss of CD22 on B cells. CBA/Ca mice and gene-targeted CD22-deficient mice on a C57BL/6 background are both similarly susceptible to pneumococcal infection, as shown by bacterial replication in the lungs, high bacteremia and early death. After bacterial infections, CD22-deficient mice had strongly reduced B cell populations in the lung, including GM-CSF producing, IgM secreting innate response activator B cells, which are crucial for protection. This study provides striking evidence that CD22 is crucial for protection during invasive pneumococcal disease.

Identifiants

pubmed: 32324805
doi: 10.1371/journal.ppat.1008464
pii: PPATHOGENS-D-19-01231
pmc: PMC7179836
doi:

Substances chimiques

Sialic Acid Binding Ig-like Lectin 2 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e1008464

Subventions

Organisme : Medical Research Council
ID : G0501416
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_U142684174
Pays : United Kingdom

Déclaration de conflit d'intérêts

The authors have declared that no competing interests exist.

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Auteurs

Vitor E Fernandes (VE)

Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, United Kingdom.

Giuseppe Ercoli (G)

Department of Genetics, University of Leicester, Leicester, United Kingdom.

Alan Bénard (A)

Department of Surgery, University Hospital Erlangen, Erlangen, Germany.

Carolin Brandl (C)

Division of Genetics, Department of Biology, University of Erlangen, Erlangen, Germany.

Hannah Fahnenstiel (H)

Division of Genetics, Department of Biology, University of Erlangen, Erlangen, Germany.

Jennifer Müller-Winkler (J)

Division of Genetics, Department of Biology, University of Erlangen, Erlangen, Germany.

Georg F Weber (GF)

Department of Surgery, University Hospital Erlangen, Erlangen, Germany.

Paul Denny (P)

Mammalian Genetics Unit, Medical Research Council, Harwell, United Kingdom.

Lars Nitschke (L)

Division of Genetics, Department of Biology, University of Erlangen, Erlangen, Germany.

Peter W Andrew (PW)

Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, United Kingdom.

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