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Published on: February 23, 2014
Differential PsaA-, PspA-, PspC-, and PdB-specific immune responses in a mouse model of pneumococcal carriage
Ravichandran Palaniappan1, Shailesh Singh, Udai P Singh
1Department of Pharmaceutical Sciences, Southern School of Pharmacy, Atlanta, GA 30310-1495, USA.
Abstract:
Larger numbers of pneumococci were detected in the nasal tract compared to the lung, cervical lymph nodes, and spleen 1, 2, 4, 7, 14, and 21 days after nasal challenge with Streptococcus pneumoniae strain EF3030. In this mouse model of pneumococcal carriage, peripheral S. pneumoniae pneumococcal surface adhesin A (PsaA)-specific humoral responses (immunoglobulin G2a [IgG2a] >> IgG1 = IgG2b > IgG3) were significantly higher than pneumococcal surface protein A (PspA)-specific, genetic toxoid derivative of pneumolysin (PdB)-specific, or pneumococcal surface protein C (PspC)-specific serum antibody levels. However, PspA-specific mucosal IgA antibody levels were significantly higher than those against PsaA, PdB, and PspC. In general, both PsaA- and PspA-specific lung-, cervical lymph node-, nasal tract-, and spleen-derived CD4(+) T-cell cytokine (interleukin-4, interleukin-6, granulocyte-macrophage colony-stimulating factor, gamma interferon, and tumor necrosis factor alpha) and proliferative responses were higher than those for either PspC or PdB. Taken together, these findings suggest that PsaA- and PspA-specific mucosal responses as well as systemic humoral and T helper cell cytokine responses are predominantly yet differentially induced during pneumococcal carriage.
Insights
This study shows Streptococcus pneumoniae colonizes the nasal tract more than other organs in mice. Immune responses to pneumococcal surface adhesin A (PsaA) and pneumococcal surface protein A (PspA) were prominent during carriage.
Area of Science:
- Immunology
- Microbiology
- Infectious Diseases
Background:
- Streptococcus pneumoniae causes significant respiratory illness.
- Understanding pneumococcal carriage is crucial for developing effective vaccines and treatments.
- The immune response during pneumococcal carriage is not fully understood.
Purpose of the Study:
- To investigate the immune response during pneumococcal carriage in a mouse model.
- To compare the induction of humoral and cellular immunity against key pneumococcal antigens.
Main Methods:
- Mice were nasally challenged with Streptococcus pneumoniae strain EF3030.
- Pneumococci colonization was quantified in nasal tract, lung, lymph nodes, and spleen.
- Humoral (serum antibody) and mucosal (IgA) responses to PsaA, PspA, PdB, and PspC were measured.
- CD4+ T-cell cytokine production and proliferative responses were assessed in various tissues.
Main Results:
- Higher pneumococcal loads were observed in the nasal tract compared to other tissues.
- Pneumococcal surface adhesin A (PsaA)-specific IgG responses were dominant systemically.
- Pneumococcal surface protein A (PspA)-specific mucosal IgA responses were significantly higher than other antigen-specific mucosal responses.
- Both PsaA- and PspA-specific CD4+ T-cell responses were elevated in multiple tissues.
Conclusions:
- Pneumococcal carriage predominantly induces PsaA- and PspA-specific immune responses.
- Systemic humoral and T helper cell responses are differentially induced during carriage.
- These findings highlight the importance of PsaA and PspA in the host-pathogen interaction during pneumococcal colonization.
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