Cross-protective mucosal immunity mediated by memory Th17 cells against Streptococcus pneumoniae lung infection

Abstract

Pneumonia caused by Streptococcus pneumoniae (Sp) remains a leading cause of serious illness and death worldwide. Immunization with conjugated pneumococcal vaccine has lowered the colonization rate and consequently invasive diseases by inducing serotype-specific antibodies. However, many of current pneumonia cases result from infection by serotype strains not included in the vaccine. In this study, we asked if cross-protection against lung infection by heterologous strains can be induced and investigated the underlying immune mechanism. We found that immune mice recovered from a prior infection were protected against heterologous Sp strains in the pneumonia challenge model, as evident by accelerated bacterial clearance, reduced pathology and apoptosis of lung epithelial cells. Sp infection in the lung induced strong Th17 responses at the lung mucosal site. Transfer of CD4+ T cells from immune mice provided heterologous protection against pneumonia, and this protection was abrogated by IL-17A blockade. Transfer of memory CD4+ T cells from IL-17A knockout mice failed to provide protection. These results indicate that memory Th17 cells played a key role in providing protection against pneumonia in a serotype independent manner and suggest the feasibility of developing a broadly protective vaccine against bacterial pneumonia by targeting mucosal Th17 T cells.

A Combination of Recombinant Mycobacterium bovis BCG Strains Expressing Pneumococcal Proteins Induces Cellular and Humoral Immune Responses and Protects against Pneumococcal Colonization and Sepsis

“…We also demonstrated that this protective immune response is mediated by Th17 CD4 ϩ T cells (19,20). Supporting these findings, another group found that transferred CD4 ϩ T cells from mice that resolved a prior pneumococcal lung infection promote a strong Th17 CD4 ϩ recall response and protect mice against pulmonary challenge with heterologous pneumococcal strains (21). These data suggest the potential use of conserved pneumococcal proteins able to induce a Th17 response that could induce protection against colonization and cooperate against invasive disease.…”

Respiratory Barrier as a Safeguard and Regulator of Defense Against Influenza A Virus and Streptococcus pneumoniae

“…T H 17 immunity promotes accelerated bacterial clearance in the URT following a secondary infection with S. pneumoniae (144). Considering that type I IFN inhibits T H 17 activation (145) and thus the generation of memory cells, influenza may prevent T H 17mediated protection against subsequent infections with the same or heterologous pneumococcal serotypes (144,187,188).…”

The roles of resident, central and effector memory CD4 T‐cells in protective immunity following infection or vaccination

“…For example, interferon (IFN)-c from CD4 T-cells protects against viral infections, while interleukin (IL)-17 aids controls of bacterial and fungal infections, and IL-4 protects against infection by parasitic worms. [12][13][14][15][16][17][18][19][20] Most immune protection studies are carried out in animal models where challenge studies are feasible and mechanisms of protection can be identified by loss or gain of function. Human challenge studies are, however, becoming more frequent and have also demonstrated that cytokine-producing memory CD4 T-cells correlate with reduced symptoms following pathogen challenge.…”