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

Autor: Giuseppe Ercoli, Georg F. Weber, Carolin Brandl, Jennifer Müller-Winkler, Paul Denny, Alan Bénard, Peter W. Andrew, Hannah Fahnenstiel, Lars Nitschke, Vitor E. Fernandes
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Male
Bacterial Diseases
B Cells
Pulmonology
Physiology
Sialic Acid Binding Ig-like Lectin 2
Bacteremia
medicine.disease_cause
Pathology and Laboratory Medicine
SIGLEC-G
Mice
White Blood Cells
Medizinische Fakultät
Animal Cells
Immune Physiology
hemic and lymphatic diseases
Medicine and Health Sciences
Responses
Innate
Protect
Ligand-binding
Biology (General)
Receptor
0303 health sciences
B-Lymphocytes
Mice
Inbred BALB C
030302 biochemistry & molecular biology
CD22
Pneumococcus
Bacterial Pathogens
Body Fluids
Pneumococcal infections
medicine.anatomical_structure
Streptococcus pneumoniae
Infectious Diseases
Blood
Medical Microbiology
Host-Pathogen Interactions
Female
Cellular Types
Pathogens
Anatomy
Research Article
QH301-705.5
Immune Cells
Immunology
Spleen
Biology
Microbiology
Pneumococcal Infections
Sepsis
Roles
03 medical and health sciences
Virology
Streptococcal Infections
medicine
Genetics
Animals
Humans
ddc:610
Antibody-Producing Cells
Molecular Biology
Gene
Microbial Pathogens
B cell
030304 developmental biology
Blood Cells
Bacteria
Organisms
Biology and Life Sciences
Streptococcus
Escherichia Coli Infections
GM-CSF
Cell Biology
Pneumonia
Pneumococcal
RC581-607
medicine.disease
Mice
Inbred C57BL
Susceptibility
Genetic Loci
Respiratory Infections
Mice
Inbred CBA
Negative regulator
Parasitology
Immunologic diseases. Allergy
Zdroj: PLoS Pathogens, Vol 16, Iss 4, p e1008464 (2020)
PLoS Pathogens
Repositório Científico de Acesso Aberto de Portugal
Repositório Científico de Acesso Aberto de Portugal (RCAAP)
instacron:RCAAP
ISSN: 1553-7374
1553-7366
Popis: 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.
Author summary Streptococcus pneumoniae (known as the pneumococcus) is a human bacterial pathogen responsible for diseases such as pneumonia and sepsis, that cause illness and death in millions of individuals. Susceptibility to pneumococcal infections is associated with genetic components that strongly influence how infected individuals respond to infection, but little is known about the causal gene(s) and the mechanisms of control of the infection. In previous studies we have found strong differences in susceptibility and resistance to pneumococcal infections between mouse strains. In this study we identified a gene, the Cd22 gene, that controls resistance to pneumococcal infection. Mice without the B-cell specific CD22 protein were much more susceptible to infection with S. pneumoniae. We could show that a protective population of B cells that migrates to the lung during pneumococcal infection is missing in Cd22-deficient mice. The study shows to a new role for CD22 and indicates a new potential target for treatment of pneumococcal infections.
Databáze: OpenAIRE
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