Nasopharyngeal colonization with Streptococcus pneumoniae triggers dendritic cell dependent antibody responses against invasive disease in mice

Abstract

Nasopharyngeal colonization with Streptococcus pneumoniae (Spn) is an important precondition for the development of pneumococcal pneumonia. At the same time, nasopharyngeal colonization with Spn has been shown to mount adaptive immune responses against Spn in mice and humans. Cellular responses of the nasopharyngeal compartment, including the nasal-associated lymphoid tissue, to pneumococcal colonization and their importance for developing adaptive immune responses are poorly defined. We show that nasopharyngeal colonization with S. pneumoniae led to substantial expansion of dendritic cells (DCs) both in nasopharyngeal tissue and nasal-associated lymphoid tissue of mice. Depletion of DCs achieved by either diphtheria toxin (DT) treatment of chimeric zDC mice, or by use of FMS-like tyrosine kinase 3 ligand (Flt3L) KO mice exhibiting congenitally reduced DC pool sizes, significantly diminished antibody responses after colonization with Spn, along with impaired protective immunity against invasive pneumococcal disease. Collectively, the data show that classical DCs contribute to pneumococcal colonization induced adaptive immune responses against invasive pneumococcal disease in two different mouse models. These data may be useful for future nasopharyngeal vaccination strategies against pneumococcal diseases in humans.

Mouse IgG2a antibodies specific for the commensalStreptococcus mitisshow stronger cross-reactivity withStreptococcus pneumoniaethan IgG1 antibodies

“…On the other hand, mouse IgG1 antibodies, which represent the equivalent of human IgG4 antibodies that plays a role in defense against S. pneumoniae, have been shown to increase in response to nasopharyngeal colonization by S. pneumoniae. 8,12 This is in accordance with our results that the S. mitis immunization gives rise to enhanced IgG1 responses reactive to S. pneumoniae. But the cross-reactivity induced by IgG1 antibodies was weaker than IgG2a antibodies.…”

“…6,7 Furthermore, nasopharyngeal colonization of mice with S. pneumoniae triggers a significant rise in the levels of antigen-specific IgG2a and IgG1 antibodies. 8 It however remains unknown whether S. mitis-specific IgG antibody responses that are crossreactive to S. pneumoniae are biased to an IgG subclass, such as IgG2a and IgG1.…”

Colonization‐induced protection against invasive pneumococcal disease in mice is independent of CD103 driven adaptive immune responses

“…Recently, we have shown that depletion of classical DC attenuated nasopharyngeal colonization‐induced systemic and mucosal antibody responses, and hence protection from IPD in mice . Based on these findings, in the current study, we aimed to dissect the contribution of integrin αE (CD103) on colonization‐induced antibody responses in WT and CD103 KO mice as well as Batf3 KO mice (Fig.…”

“…The Gram‐positive bacterium Streptococcus pneumoniae is a colonizing commensal of the nasopharyngeal compartment. Nasopharyngeal colonization with S. pneumoniae has been found to trigger protective immune responses both in humans and mice . At the same time, pneumococcal colonization of the nasopharynx may also be a ‘starting point’ for upper and lower respiratory tract infections, including otitis media as well as community‐acquired pneumonia (CAP) with or without septic disease progression, mainly (but not exclusively) in infants, the elderly and immunocompromised individuals .…”

“…We have recently shown that classical dendritic cells play an important role in pneumococcal colonization‐induced adaptive immunity in mice . Depletion of dendritic cells led to significantly attenuated anti‐pneumococcal antibody responses and impaired protective immunity against invasive pneumococcal disease in mice . In the respiratory system, the majority of classical DC is comprised of CD11b pos , CD103 neg DC, as well as CD103 pos , CD11b neg DC.…”