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.

Hemolytic potential of bioaerosol-derived Aspergillus, Penicillium and Talaromyces mould isolates

“…Hemolysins have been defined as exotoxins, capable of lysing erythrocytes as well as nucleated cells, and these compounds are able to interact with specific ligands on the surface of various target cells (Nayak et al, 2013). During the lysis of red blood cells the iron is released, which is an important growth factor for microbes especially during infection (Subramanian et al, 2014). For some fungal isolates which display positive hemolytic activity in this study, the hemolysins have been discovered and characterized.…”

“…Two types of hemolysis are described: (I) complete (β) hemolysis, which represents total erythrocyte destruction by extracellular metabolites of microorganisms, and (II) partial (α) hemolysis as a result of the oxidation of hemoglobin (Fe 2+ ) to methemoglobin (Fe 3+ ) and ferry hemoglobin (Fe 4+ ); while absence of hemolysis is self-contradictory called γ hemolysis (Buxton, 2005). Upon erythrocyte lysis, free hemoglobin and/or heme are released from the cell and pathogens employ various mechanisms to utilize iron contained in these molecules (Bullard et al, 2012;Subramanian et al, 2014). The ability of pathogens to acquire iron has been documented to be of the upmost importance for their survival within the mammalian host cells, and further, ability to cause infection (Aktas and Yigit, 2014).…”