Vaccination using inactivated Mycoplasma pneumoniae induces detrimental infiltration of neutrophils after subsequent infection in mice

Mycoplasma pneumoniae (Mp) is one of the most common causes of community-acquired pneumonia. Given the emergence and high rates of antibiotic-resistant Mp strains, vaccines that prevent the pneumonia and secondary complications due to Mp infection are urgently needed. Although several studies have shown the protective efficacy of Mp vaccines in human clinical trials, some reports suggest that vaccination against Mp exacerbates disease upon subsequent Mp challenge. Therefore, to develop optimal vaccines against Mp, understanding the immune responses that contribute to post-vaccination exacerbation of inflammation is crucial. Here we examined whether Mp vaccination might exacerbate pneumonia after subsequent Mp infection in mice. We found that vaccination with inactivated Mp plus aluminum salts as an adjuvant induced Mp-specific IgG, Th1 cells, and Th17 cells. Toll-like receptor 2 signaling contributed to the induction of an Mp-specific IgG response and was necessary for Mp-specific Th17-cell-but not Th1-cell-responses in vaccinated mice. In addition, vaccination with inactivated Mp plus aluminum salts suppressed the number of Mp organisms in the bronchoalveolar lavage fluid, indicating that vaccination can reduce Mp infection. However, the numbers of total immune cells and neutrophils in bronchoalveolar lavage fluid after Mp challenge did not differ between vaccinated mice and non-vaccinated control mice. Furthermore, depletion of CD4(+) T cells prior to Mp challenge decreased pulmonary neutrophil infiltration in vaccinated mice, suggesting that Th1 or Th17 cells (or both) are responsible for the vaccination-induced neutrophil infiltration. These results suggest that, despite reducing Mp infection, vaccination of mice by using inactivated Mp fails to suppress inflammation, such as neutrophil infiltration into the lung, after subsequent Mp infection. (C) 2020 Elsevier Ltd. All rights reserved.