Thus, these results demonstrated that neutrophils, F4/80+ macrophages and Selleckchem LY2157299 Gr-1dull+ CD11c+ macrophage-like cells played an important role in the production of TNF-α in lungs at an early stage of infection with S. pneumoniae. Streptococcus pneumoniae, an extracellular Gram-positive diplococcus,

most frequently causes community-acquired pneumonia, which leads to severe pneumonia, bacteremia and meningitis in infants, elderly people and patients with underlying diseases such as chronic cardiopulmonary diseases, diabetes mellitus, liver cirrhosis, hematological malignancies, HIV infection and splenectomy. Moreover, penicillin-resistant S. pneumoniae has

spread worldwide and has become a problem in the treatment of patients. Thus, it is strongly recommended that high-risk individuals receive the pneumococcal polysaccharide vaccine (Marrie, 1999; Gant & Parton, 2000). Pneumonia caused by this bacterium is associated with massive infiltration of neutrophils into the alveolar spaces, which provides a major contribution to the host defense via an oxygen radical-mediated killing mechanism (Musher et al., 1996). Recently, we have demonstrated that natural killer T cells and γδ T cells acted upstream the neutrophilic inflammatory responses in lungs after infection LY2606368 in vivo with S. pneumoniae (Kawakami et al., 2003; Nakamatsu et al., 2007; Nakasone et al., 2007). Mice defective in these innate immune lymphocytes were highly susceptible to this infection, which was associated with the reduced production of tumor necrosis factor (TNF)-α and attenuated recruitment of neutrophils. This cytokine

is known to facilitate the adhesion of neutrophils to vascular endothelial cells by enhancing the expression of certain adhesion molecules (Mackay et al., 1993; Collins et al., 1995) and also acts to promote their killing activity against infectious microorganisms (Ferrante et al., 1993; Broug-Holub Chlormezanone et al., 1997). TNF-α is reported to play a critical role in the host defense to S. pneumoniae, as shown by the exacerbated infection in mice treated with monoclonal antibody (mAb) against this cytokine (van der Poll et al., 1997; Rijneveld et al., 2001). Although TNF-α is known to be produced by macrophages and dendritic cells upon stimulation with various Toll-like receptor ligands (Beutler & Cerami, 1989), the cellular source of this cytokine after infection with this bacterial pathogen remains to be fully understood. Recently, we have identified CD11bbright+ cells as its candidate (Nakamatsu et al., 2007), which may include macrophages, dendritic cells and neutrophils (Gonzalez-Juarrero et al., 2003).