Phagocyte Recognition of Microbes (Nakayama Group)
Phagocytes such as macrophages and dendritic cells (DC) recognize and engulf microbes and apoptotic cells. We focus on the molecular mechanisms by which phagocytes recognize such pathogenic particles on their cell surfaces. So far, we have identified the paired receptors for Gram-positive Staphylococcus aureus （Nakayama et al., J. Immunol., 2007; Nakayama et al., J. Immunol., 2012）. As a phosphatidylserine receptor on DC1, we have identified Tim-3, which is critical for phagocytosis of apoptotic cells and cross-presentation (Nakayama et al., Blood, 2009).
Macrophage Recognition of Environmental Particles and Crystals (Nakayama Group)
Today our bodies are exposed to environmental particles such as PM2.5, silica, and engineered nanoparticles. When these particles enter the body, many of them are recognized by macrophages and provoke inflammation, which could cause incurable diseases. For instance, silica and asbestos are well known to cause silicosis and mesothelioma, resepepctively. Carbon nanotubes, highly representative products of nanotechnology, may have asbestosis-like pathogenicity. We are interested in understanding how macrophages recognize such inorganic particles. So far, we have identified class B scavenger receptor SR-B1 for silica （Tsugita et al., Cell Rep., 2017） and Tim4 for carbon nanotubes (Omori et al., Cell Rep., 2021).
Trogocytosis Shapes Immune Responses (Nakayama Group)
The term trogocytosis is from the ancient Greek Trogo, meaning “to bite”, which is a process by which a cell acquires plasma membrane fragments from a neighbor cell in a cell-cell contact-dependent manner. We are interested in understanding how trogocytosis shapes immune responses. So far, we have revealed that MHC trogocytosis regulates NK cell and CD4 T cell function (Nakayama, Front. Immunol., 2015; Nakamura et al., PNAS, 2013; Nakayama et al., PNAS, 2011). Trogocytosis is considered to be involved in various immune responses and diseases such as cancer, infection, and autoimmune diseases. However, many things about this new phenomenon still remain unknown.
Modulation of Neutrophil Function (Noyori Group)
Neutrophils, innate immune phagocytes, have central roles in host defense especially in bacterial clearance. But, adverse functions, as dual roles, are known in mediating tissue damages, for example, by uncontrollable secretion of granules.
Hence, controlling the neutrophil activation state during infection is pivotal. Our goal of this study is to unveil the mechanisms regulating neutrophil activation state “On” and “Off” and obtain the approaches for their therapeutic modulation. Currently, we are focusing on the functional analysis of purinergic receptors expressing on the neutrophils.
Pathogen Transmission through protruded structure formed in infected cells (Noyori Group)
In 1918 Spanish flu and 2009 pandemic, a number of patients died of severe pneumonia caused by flu and bacteria co-infection. In the current study, we found that alveolar epithelial cells, in the co-infection of flu and bacteria, formed a number of protruded structures that were extended from the plasma membrane and connected with distant cells. It has been reported to date that some pathogens such as HIV-1 and prion are known to facilitate their transmission through the manipulation of infected cells to form this unique protruded-cell structure, called tunneling nanotube, with several cell diameters in length, which would be connected with uninfected cells. This “Hijack “of cells is considered as a phenomenon involved in the pathogenicity. We would like to unveil the mechanisms underlying the formation of this unique structure based on molecular biology and know the biological function of this in terms of pathogenicity.