Antigen-Independent Restriction of Pneumococcal Density by Mucosal Adjuvant Cholera Toxin Subunit B.
For many bacterial respiratory infections, development of (severe) disease is preceded by asymptomatic colonization of the upper airways. For Streptococcus pneumoniae, the transition to severe lower respiratory tract infection is associated with an increase in nasopharyngeal colonization density. Insight into how the mucosal immune system restricts colonization may provide new strategies to prevent clinical symptoms. Several studies have provided indirect evidence that the mucosal adjuvant cholera toxin subunit B (CTB) may confer nonspecific protection against respiratory infections. Here, we show that CTB reduces the pneumococcal load in the nasopharynx, which required activation of the caspase-1/11 inflammasome, mucosal T cells, and macrophages. Our findings suggest that CTB-dependent activation of the local innate response synergizes with noncognate T cells to restrict bacterial load. Our study not only provides insight into the immunological components required for containment and clearance of pneumococcal carriage, but also highlights an important yet often understudied aspect of adjuvants.
Laboratory of Pediatric Infectious Diseases.
Kirsten
K
Kuipers
Laboratory of Pediatric Infectious Diseases.
Dimitri A
DA
Diavatopoulos
Laboratory of Pediatric Infectious Diseases.
Fred
F
van Opzeeland
Laboratory of Pediatric Infectious Diseases.
Elles
E
Simonetti
Laboratory of Pediatric Infectious Diseases.
Corné H
CH
van den Kieboom
Laboratory of Pediatric Infectious Diseases.|Department of Internal Medicine, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen.
Mariska
M
Kerstholt
Laboratory of Pediatric Infectious Diseases.|Necki Institute of Experimental Biology, Warsaw, Poland.
Malgorzata
M
Borczyk
Laboratory of Pediatric Oncology, Department of Pediatrics.
D
D
van IngenSchenau
Department of Pediatrics, University Medical Center Groningen, The Netherlands.
Eelke T
ET
Brandsma
Department of Internal Medicine, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen.
Mihai G
MG
Netea
Laboratory of Pediatric Infectious Diseases.
Marien I
MI
de Jonge
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology*; D058956:Administration, Mucosal; D000818:Animals; D000941:Antigens; D000942:Antigens, Bacterial / Q000032:analysis*; D058491:Bacterial Load; D002353:Carrier State / Q000276:immunology*; D002772:Cholera Toxin / Q000008:administration & dosage / Q000494:pharmacology*; D058847:Inflammasomes / Q000378:metabolism; D008264:Macrophages / Q000276:immunology; D008810:Mice, Inbred C57BL; D009305:Nasopharynx / Q000382:microbiology; D011008:Pneumococcal Infections / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000276:immunology / Q000302:isolation & purification*; D013601:T-Lymphocytes / Q000276:immunology
D000276:Adjuvants, Immunologic; D000941:Antigens; D000942:Antigens, Bacterial; D058847:Inflammasomes; D002772:Cholera Toxin
Streptococcus pneumoniae; T cells; bacterial colonization; bacterial density; cholera toxin subunit B; inflammasome; macrophages; mucosal adjuvant