Role of basophils in immunological memory responses to pneumococcal protein antigens and S. pneumoniae infections in mice

Introduction: We have shown recently that basophils play an important role in enhancing secondary humoral memory immune responses to intact pneumococcal protein antigen, thereby markedly improving survival in a mouse model of pneumococcal sepsis. We here investigated the effect of expanded basophil pool sizes on immunization efficacies against S. pneumoniae in mice.

Methods: Mice underwent primary and secondary immunization with the pneumococcal surface protein A (PspA). Basophil pool sizes were expanded immediately prior to secondary immunization by treatment with IL-3 or IL-3 complexed with anti-IL-3 antibody. Subsequently, PspA-specific antibody titers were determined and survival of mice infected with highly virulent S. pneumoniae was monitored.

Results: Treatment of mice with IL-3 and even more so with IL-3 complexed with anti-IL-3 antibody (IL-3 complex) resulted in strongly expanded basophil pool sizes in blood, spleen and bone marrow of mice. Moreover, such increased basophil counts in PspA-immunized mice pretreated with IL-3 complex resulted in significantly increased PspA-specific IgG1 and IgG2a antibody titers in plasma of mice. However, such increased humoral immune responses to PspA observed in IL-3 complex pretreated mice failed to protect mice from lethal pneumococcal lung infection. At the same time, passive immunization of mice with PspA-specific antiserum collected from IL-3 complex treated, PspA immunized mice significantly improved their survival after challenge with highly invasive S. pneumoniae.

Discussion: IL-3 complex treatment to enhance basophil pool sizes in mice immunized with intact pneumococcal protein antigen does not offer as adjuvant-independent approach to enhance basophil-dependent humoral memory immune responses against S. pneumoniae in mice, which may be due to severe side effects of the IL-3 pretreatment maneuver.