Abstract
Recent studies have identified a clinical isolate of the commensal Streptococcus mitis that expresses Streptococcus pneumoniae serotype 5 capsule (S. mitis serotype 5) and shows serospecificity toward pneumococcal serotype 5. However, it remains unknown whether S. mitis serotype 5 induces protective immunity against pneumococcal serotype 5. In this study, we evaluated the ability of S. mitis serotype 5 to generate protective immunity in a mouse model of lung infection with pneumococcal serotype 5. Upon challenge infection with S. pneumoniae serotype 5, mice intranasally immunized with S. mitis serotype 5 exhibited reduced pneumococcal loads in the lungs, nasal wash, and bronchoalveolar lavage fluid compared with those receiving PBS (control). The immunized mice displayed significantly higher levels of IgG and IgA antibodies reactive to S. mitis serotype 5, S. pneumoniae serotype 5 or S. pneumoniae serotype 4 than the antibody levels in control mice. In vaccinated mice, the IgG/IgA antibody levels reactive to S. mitis serotype 5 or S. pneumoniae serotype 5 were higher than the levels reactive to S. pneumoniae serotype 4. Furthermore, in-vitro restimulation of the lung-draining mediastinal lymph node cells and splenocytes from immunized mice with killed S. mitis serotype 5, S. pneumoniae serotype 5 or S. pneumoniae serotype 4 showed enhanced Th17, but not Th1 and Th2, responses. Overall, our findings show that mucosal immunization with S. mitis serotype 5 protects against S. pneumoniae serotype 5 infection and induces Th17 and predominant serotype-specific IgG/IgA antibody responses against pneumococcal infection.
Highlights
Streptococcus pneumoniae is an important human pathogen that causes a range of diseases, including sepsis, meningitis, and pneumonia, and poses a threat to public health worldwide [1, 2]
In line with the findings from the lymph node cell restimulation (Figure 4A), we found that Th17, but not Th1 and Th2, cytokine levels produced by the splenocytes restimulated with S. mitis serotype 5, S. pneumoniae 5 or S. pneumoniae 4 were significantly increased compared with the cytokine levels in control mice (Figure 4B)
Our present study supports this hypothesis because intranasal immunization of mice with S. mitis serotype 5 triggered protective immunity against nasal colonization by and lung infection with S. pneumoniae serotype 5
Summary
Streptococcus pneumoniae is an important human pathogen that causes a range of diseases, including sepsis, meningitis, and pneumonia, and poses a threat to public health worldwide [1, 2]. S. mitis-Induced Immunity to S. pneumoniae polysaccharides are considered to be the most important virulence factor by protecting pneumococci from immune cellmediated phagocytosis. More than 90 serotypes have far been reported [4] Out of these pneumococcal serotypes, serotype 5 is strongly associated with invasive pneumococcal disease (IPD), with an invasiveness index that is 60 times higher than those of some of the least invasive serotypes [7, 8]. This serotype is contained in pneumococcal conjugate vaccine (PCV) and pneumococcal polysaccharide vaccine (PPSV) formulations
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