AUTHOR=Kim Kwang H. , Park Donghwan , Cho Soo Young , Cho Yejin , Lee Buhyun , Jeong Haengdueng , Lee Yura , Lee Yourim , Nam Ki Taek 

TITLE=Role of histamine-mediated macrophage differentiation in clearance of metastatic bacterial infection

JOURNAL=Frontiers in Immunology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1290191

DOI=10.3389/fimmu.2023.1290191

ISSN=1664-3224

ABSTRACT=<p>Macrophages are highly heterogeneous immune cells with a role in maintaining tissue homeostasis, especially in activating the defense response to bacterial infection. Using flow cytometric and single-cell RNA-sequencing analyses of peritoneal cells, we here show that small peritoneal macrophage and immature macrophage populations are enriched in histamine-deficient (<italic>Hdc</italic><sup>-/-</sup>) mice, characterized by a CD11b<sup>mi</sup>F4/80<sup>lo</sup>CCR2<sup>+</sup>MHCII<sup>hi</sup> and CD11b<sup>lo</sup>F4/80<sup>mi</sup>THBS1<sup>+</sup>IL-1α<sup>+</sup> phenotype, respectively. Molecular characterization revealed that immature macrophages represent an abnormally differentiated form of large peritoneal macrophages with strong inflammatory properties. Furthermore, deficiency in histamine signaling resulted in significant impairment of the phagocytic activity of peritoneal macrophage populations, conferring high susceptibility to bacterial infection. Collectively, this study reveals the importance of histamine signaling in macrophage differentiation at the molecular level to maintain tissue homeostasis, offering a potential therapeutic target for bacterial infection-mediated diseases.</p>