title: Preferential silent survival of intracellular bacteria in hemoglobin-primed macrophages.
abstract: Hemolysis releases hemoglobin (Hb), a prooxidant, into circulation. While the heme iron is a nutrient for the invading pathogens, it releases ROS, which is both microbicidal and cytotoxic, making it a double-edged sword. Previously, we found a two-pass detoxification mechanism involving the endocytosis of Hb into monocytes in collaboration with vascular endothelial cells to overcome oxidative damage. This prompted us to examine the effect of Hb priming on host cell viability and intracellular bacterial clearance during a hemolytic infection. Here, we demonstrate that Hb-primed macrophages harbor a higher intracellular bacterial load but with suppressed apoptosis. p-ERK and p-p38 MAPK were significantly downregulated, with concomitant impairment of Bax and downstream caspases. The Hb-primed cells harboring intracellular bacteria upregulated anti-inflammatory IL-10 and downregulated proinflammatory TNF-α, which further enhanced the infectivity of the neighboring cells. Our findings suggest that opportunistic intracellular pathogens exploit the Hb-scavenging machinery of the host to silently persist within the circulating phagocytes by suppressing apoptosis while escaping immune surveillance.
authors.affiliation: Department of Biological Sciences, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
authors.forename: Karthik
authors.initials: K
authors.lastname: Subramanian
authors.forename: Imelda
authors.initials: I
authors.lastname: Winarsih
authors.forename: Chandrakumaran
authors.initials: C
authors.lastname: Keerthani
authors.forename: Bow
authors.initials: B
authors.lastname: Ho
authors.forename: Jeak Ling
authors.initials: JL
authors.lastname: Ding
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001424:Bacterial Infections / Q000276:immunology*; D058491:Bacterial Load / Q000187:drug effects; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006454:Hemoglobins / Q000494:pharmacology*; D006461:Hemolysis / Q000276:immunology; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D042541:Intracellular Space; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology; D016877:Oxidants / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D006454:Hemoglobins; D016877:Oxidants; D014409:Tumor Necrosis Factor-alpha; D051028:bcl-2-Associated X Protein; D016753:Interleukin-10; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D020169:Caspases