Abstract
Streptococcus pneumoniae may colonize the nasopharynx, and as pneumococcal colonization causes invasive diseases and the subsequent transmission, reducing bacterial burden in the nasal cavity is critical. Hochu-ekki-to (TJ-41) is a traditional Japanese herbal medicine that exerts immunomodulatory effects in host cells. In this study, we investigated the potency of TJ-41 in modulating pneumococcal colonization clearance by activating host immunity. Mice, intranasally inoculated with pneumococci, were treated orally with TJ-41. During colonization, TJ-41 treatment significantly reduced pneumococcal burden and increased macrophage population in the nasopharynx. Furthermore, interleukin 17A production was significantly enhanced after TJ-41 treatment. In vitro experiment using nasal-derived cells revealed that pneumococcal antigen exposure upregulated the transcription of interleukin 17A in the TJ-41-treated group compared with that in the control group. Macrophages activated by killed bacteria were significantly increased in the presence of TJ-41 in an interleukin 17A-dependent manner. Moreover, TJ-41 enhanced phagocytosis, inhibited bacterial growth, and improved the antigen-presenting capacity of macrophages. Our results demonstrate that TJ-41 accelerates the clearance of pneumococcal nasopharyngeal colonization via macrophage activation. Subsequent production of interleukin 17A provides an additional benefit to effector cells.
Highlights
Streptococcus pneumoniae, a gram-positive coccus, is a major cause of pneumonia, meningitis, and sepsis
An examination of the transitional change in bacterial load in the nasal cavity of the pneumococcal colonization model revealed that it was slightly decreased, colonization in the nasal cavity was confirmed during the period of examination (Supplementary Figure 2)
The results suggest that TJ-41 has a positive effect on pneumococcal colonization clearance
Summary
Streptococcus pneumoniae, a gram-positive coccus, is a major cause of pneumonia, meningitis, and sepsis. Pneumococcal diseases impose a heavy burden on global health with high morbidity and mortality rates (Weiser et al, 2018). Pneumococcal vaccines have preventive effects against pneumococcal diseases (Pilishvili et al, 2010; Bonten et al, 2015; Suga et al, 2015). It has been reported that diseases caused by vaccine-uncovered serotypes account for a higher portion of the total pneumococcal diseases, termed “serotype replacement” (Balsells et al, 2017). There is a need for preventive strategies for pneumococcal infections. Pneumococci generally invade human nasopharynx and establish colonization. This is a prerequisite for invasive diseases (Bogaert et al, 2004). Colonized individuals may act as reservoirs for inter-individual transmission of pneumococci (Kadioglu et al, 2008; Wolter et al, 2014), warranting the control of pneumococcal nasopharyngeal colonization
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