Abstract
The phagocyte respiratory burst is crucial for innate immunity. The transfer of electrons to oxygen is mediated by a membrane-bound heterodimer, comprising gp91phox and p22phox subunits. Deficiency of either subunit leads to severe immunodeficiency. We describe Eros (essential for reactive oxygen species), a protein encoded by the previously undefined mouse gene bc017643, and show that it is essential for host defense via the phagocyte NAPDH oxidase. Eros is required for expression of the NADPH oxidase components, gp91phox and p22phox Consequently, Eros-deficient mice quickly succumb to infection. Eros also contributes to the formation of neutrophil extracellular traps (NETS) and impacts on the immune response to melanoma metastases. Eros is an ortholog of the plant protein Ycf4, which is necessary for expression of proteins of the photosynthetic photosystem 1 complex, itself also an NADPH oxio-reductase. We thus describe the key role of the previously uncharacterized protein Eros in host defense.
Highlights
Infectious diseases cause major morbidity and mortality worldwide
Typhimurium () In this study, we show that mice deficient in a previously uncharacterized gene, bc017643, are highly susceptible to Salmonella and Listeria infection and are impaired in their ability to control replication of either pathogen.We show that this is because bc017643 encodes a gene, which we name essential for reactive oxygen species (Eros), that is necessary for the phagocyte respiratory burst
Mice harboring a targeted mutation in bc017643, a previously uncharacterized protein-coding gene located on chromosome 11 (Fig. S1 A), were highly susceptible to S.Typhimurium, dying 4–5 d after intravenous inoculation with the attenuated S.Typhimurium M525 (Fig. 1 A).As we demonstrate that bc017643 is crucial for the generation of a phagocyte respiratory burst in the innate immune system, we have renamed the gene Eros
Summary
Infectious diseases cause major morbidity and mortality worldwide. For example, specific serovars of Salmonella such as typhi and paratyphi cause typhoid fever (enteric fever), whereas nontyphi Salmonella can cause invasive systemic infection (Dougan et al, 2011; Gilchrist et al, 2015). Typhimurium provides a useful model of immunity to this bacterium and others that colonize macrophages (Chatfield et al, 1992; Conlan, 1997; Richter-Dahlfors et al, 1997; Mastroeni et al, 2000;Vazquez-Torres et al, 2000a, 2004; Burton et al, 2014).
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