Other investigations have reported several Gr-1+ mononuclear cells affecting immune responses (Bronte et al., 2000; Nakano et al., 2001; Delano et al., 2007). Bronte et al. (2000) found Gr-1+CD11b+CD31+ macrophages in the secondary lymphoid organs of immunocompromised mice that suppress the function of CD8+ T cells (designated as inhibitory macrophages). Nakano et al. (2001) reported Gr-1+CD11b−CD11c+ cells found in mouse lymph node and spleen that display characteristics of plasmacytoid

dendritic cells and produce interferon-α (IFN-α) Pictilisib in vitro after stimulation with the influenza virus. Delano et al. (2007) have recently demonstrated the dramatic increase of Gr-1+CD11b+ cells with heterogenous morphologies in the spleen, lymph nodes and bone marrow during polymicrobial sepsis, which produce inflammatory cytokines and chemokines including TNF-α, and contribute to the suppression of antigen-specific CD8+ T cell IFN-γ production and a shift from Th1- to Th2-type antibody responses. At present, the relationship between these reported cells and Gr-1dull+ cells described in the current study remains unclear. Although both Gr-1dull+ cells and neutrophils showed intracellular expression of TNF-α in a flow cytometric analysis, it is not clear as to which cell populations contributed more to the production of this cytokine in the lungs during infection with S. pneumoniae.

In this respect, the sorted Gr-1bright+ cells (neutrophils) selleckchem did not or marginally secreted TNF-α second in an in vitro culture. However, these findings may not necessarily exclude their possible contribution to the in vivo synthesis of this cytokine. In our hands, in vivo depletion of Gr-1+ cells by the specific mAb did not lead to the complete inhibition of TNF-α synthesis detected in BALF, which suggested that TNF-α production was not completely ascribed to neutrophils and Gr-1dull+ cells. We also observed the expression of this cytokine in F4/80+ cells at an earlier stage of pneumococcal infection before Gr-1dull+ cells appeared. Considered collectively, these results suggested that alveolar

macrophages may contribute in part to the synthesis of TNF-α in lungs. In conclusion, we revealed the possible involvement of neutrophils and Gr-1dull+ CD11c+ macrophage-like cells in the production of TNF-α in lungs at an early stage of infection with S. pneumoniae. TNF-α was shown to play pivotal roles in recruiting neutrophils and protecting mice from this bacterial pathogen, suggesting that this unusual subset may contribute to the host defense by inducing this cytokine. Thus, the present study provides important implications for our understanding of the pathogenic mechanism of pneumococcal infection and development of more effective vaccine strategies. Further investigations will be necessary to define the more detailed characteristics of this population and its precise role in the host-protective responses.