Laboratory of Microbial Infection and Host Immunity  

To efficiently control microbial infections, it is important to understand how pathogens infect the host and how immune system defends the host against infections. Our current research activities focus on (1) identification and characterization of microbial components causing infectious diseases, (2) elucidation of immune responses to microbial virulence factors, and (3) development of platform technology for the evaluation of vaccine efficacy.  

Research topics  

Innate immune responses to PAMPs

Bacterial infections trigger both the adaptive and innate branches of the immune system in the host. By recognizing the antigens specific to a pathogen, the adaptive immunity provides highly effective antigen-specific protection. However, it becomes relevant only during the late phase of the infection. In contrast, innate immunity protects the host during the early phase of infection by using germ-line encoded receptors to recognize the structurally conserved molecular patterns present in many pathogens. The two groups of molecules are commonly called pathogen-associated molecular pattern (PAMP) molecules and the PAMP receptors including Toll-like receptors. In addition to providing the initial protection to the host, innate immunity influences the subsequent development of adaptive immunity. In this study, we investigate the innate immune responses to PAMPs such as lipopolysaccharide (LPS), lipoteichoic acid (LTA), peptidoglycan (PGN), flagellin, and microbial nucleic acids.

Lipoteicoic acid of Gram-positive bacteria

Although microorganisms have similar cell wall structures, their pathogenecity and immunogenicity are different among strains. Accumulating reports suggest that it is because pathogenic microorganisms express different structures of PAMPs. Among the PAMPs, one of the best characterized PAMP is LPS of Gram-negative bacteria because it is a major etiologic agent for bacterial sepsis. Unlike Gram-negative bacteria, Gram-positive bacteria express not LPS but LTA in the cell wall and LTA is considered as the LPS counterpart in Gram-positive bacteria because of similarities in their structures and inflammatory potential. Notably, infections by Gram-positive bacteria get more attention in light of the fact that about 50% of all sepsis cases are caused by Gram-positive bacteria and its prevalence will be expected to continuously rise. However, the immunological properties of LTA are still controversial because the LTA used in early studies often contained biologically-active contaminants and/or was structurally-damaged during purification. In this study, we prepare highly-pure and structurally intact LTA from pathogenic and non-pathogenic bacteria and investigate the structural and functional relationships. Target bacteria are Staphylococcus aureus, Streptococcus pneumoniae, Enterococcus faecalis, Bacillus subtilis, and Lactobacillus plantarum and other bacterial species will be gradually added.

Clinical immune-monitoring of vaccines

In order to develop effective vaccines, reliable assays that can effectively evaluate vaccine efficacy are necessary. The research focuses on the development, validation, and standardization of serologic assays for measuring immune responses to vaccines in humans. In addition, this research aims at establishing reference tests for the laboratory diagnosis of enteric and respiratory infections relevant to clinical field studies. Such assays can provide surrogate markers of vaccine efficacy and are thus essential for the approval of vaccines by regulatory agencies or to prove that the vaccine can be manufactured to the same immunological potency demonstrated during research. Primary assay targets include enzyme-linked immunosorbent assay (ELISA), bactericidal assay for measuring functional antibody titers, a flow cytometry assay to characterize B and T lymphocyte subsets, ELISPOT tests for detecting antibody-producing cells or cytokine-secreting cells in human blood, colorimetric assays for measuring lymphocyte proliferation, and assays for quantifying human cytokines and chemokines. A focus in all of our work is to develop tests that are simple and robust enough to be performed under field conditions.