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Candida/Staphylococcal Polymicrobial Intra-Abdominal Infection: Pathogenesis and Perspectives for a Novel Form of Trained Innate Immunity

1
Center of Excellence in Oral and Craniofacial Biology, School of Dentistry, Louisiana State University Health Sciences Center, New Orleans, LA 70119, USA
2
Department of Microbiology and Immunology, School of Medicine, Tulane University, New Orleans, LA 70112, USA
*
Author to whom correspondence should be addressed.
J. Fungi 2019, 5(2), 37; https://doi.org/10.3390/jof5020037
Received: 15 April 2019 / Revised: 6 May 2019 / Accepted: 7 May 2019 / Published: 9 May 2019
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Abstract

Polymicrobial sepsis is difficult to diagnose and treat and causes significant morbidity and mortality, especially when fungi are involved. In vitro, synergism between Candida albicans and various bacterial species has been described for many years. Our laboratory has developed a murine model of polymicrobial intra-abdominal infection with Candida albicans and Staphylococcus aureus, demonstrating that polymicrobial infections cause high levels of mortality, while monoinfections do not. By contrast, closely related Candida dubliniensis does not cause synergistic lethality and rather provides protection against lethal polymicrobial infection. This protection is thought to be driven by a novel form of trained innate immunity mediated by myeloid-derived suppressor cells (MDSCs), which we are proposing to call “trained tolerogenic immunity”. MDSC accumulation has been described in patients with sepsis, as well as in in vivo sepsis models. However, clinically, MDSCs are considered detrimental in sepsis, while their role in in vivo models differs depending on the sepsis model and timing. In this review, we will discuss the role of MDSCs in sepsis and infection and summarize our perspectives on their development and function in the spectrum of trained innate immune protection against fungal-bacterial sepsis. View Full-Text
Keywords: Sepsis; polymicrobial; Candida; Staphylococcus; trained innate immunity; MDSC Sepsis; polymicrobial; Candida; Staphylococcus; trained innate immunity; MDSC
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Esher, S.K.; Fidel, P.L., Jr.; Noverr, M.C. Candida/Staphylococcal Polymicrobial Intra-Abdominal Infection: Pathogenesis and Perspectives for a Novel Form of Trained Innate Immunity. J. Fungi 2019, 5, 37.

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