Differential PsaA-, PspA-, PspC-, and PdB-Specific Immune Responses in a Mouse Model of Pneumococcal Carriage

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] Ͼ Ͼ 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.

Pneumococcal Interactions with Epithelial Cells Are Crucial for Optimal Biofilm Formation and Colonization In Vitro and In Vivo

“…This procedure produced a mean carriage of 5 ϫ 10 6 pneumococci per nasopharyngeal tissue after 48 h, without any evidence of disease. These numbers are in agreement with other studies using the EF3030 strain (13,55,62). Pneumococcal growth in the tissues was verified by morphology of the bacteria on blood agar plates in combination with testing several isolated clones for optochin sensitivity.…”

“…Although a role of biofilm formation during pneumococcal disease has been shown, the growth phenotype of bacteria colonizing the human nasopharynx, its main biological niche, has not been visually documented. To obtain the best chance of observing biofilm formation in vivo and to produce the most clinically relevant colonization possible, we inoculated BALB/cByJ mice intranasally for 48 h with a clinical strain of pneumococci, EF3030, that has been well documented, by us and others, to effectively establish noninvasive colonization of high bacterial density (4,55,62). This procedure produced a mean carriage of 5 ϫ 10 6 pneumococci per nasopharyngeal tissue after 48 h, without any evidence of disease.…”

Functional Characterization of the IlpA Protein of Vibrio vulnificus as an Adhesin and Its Role in Bacterial Pathogenesis

“…Mutation in the psaA gene caused pleiotropic effects on the growth, oxidative stress response, adherence, and virulence of S. pneumoniae (14). PsaA was also found to be one of the main pneumococcal antigens and causes a distinct immune response in a mouse model which is different from those mediated by other pneumococcal antigens (25). Another group of well-known bacterial adhesins are pili or fimbriae (28).…”

Genetic Diversity of PspA Types among Nasopharyngeal Isolates Collected during an Ongoing Surveillance Study of Children in Brazil

“…Briles et al (10) demonstrated that sera from PspA-immunized individ-uals protect mice from fatal infection with S. pneumoniae expressing PspAs of different families. Studies of the local and systemic immune responses against PspA have raised evidence that antibodies to PspA could prevent NP colonization in humans and mice (20,25). Thus, on the basis of its immunogenic properties, PspA could be an alternative antigen in a vaccine formulation aimed at attaining a strong impact on the prevention of pneumococcal NP colonization, in addition to protecting against invasive disease.…”