Chau Tran Bao Vu1, Arsa Thammahong2, Asada Leelahavanichkul3,4, Patcharee Ritprajak5,6. 1. Graduate Program in Oral Biology, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand. 2. Antimicrobial Resistance and Stewardship Research Unit, Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. 3. Immunology Unit, Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand. 4. Translational Research in Inflammation and Immunology Research Unit (TRIRU), Department of Microbiology, Chulalongkorn University, Bangkok, Thailand. 5. Department of Microbiology, Faculty of Dentistry, Chulalongkorn University, Bangkok, 10330, Thailand. 6. Research Unit in Integrative Immuno-Microbial Biochemistry and Bioresponsive Nanomaterials, Department of Microbiology, Chulalongkorn University, Bangkok, Thailand.
Abstract
BACKGROUND: Secondary fungal infection is a major complication in patients with sepsis-associated immunosuppression. However, sepsis-induced immune alterations related to fungal susceptibility have not been well characterized. OBJECTIVES: To determine kinetic changes in the immune phenotype by determining the proportion of T cells, B cells and macrophages, and especially the expression of an immune exhaustion marker PD-1, in murine sepsis. In addition, sepsis -induced alterations of these immune cells were assessed in relation to susceptibility to secondary fungal infection. METHODS: Cecal ligation and puncture (CLP) was used as a mouse sepsis model, with Candida albicans as the secondary systemic fungal infection. Splenic T cells, B cells and macrophages were assessed by flow cytometry. RESULTS: Alterations in T cell and B cell numbers and the proportion of PD-1 expressing T cells and B cells in CLP mice were not clearly related to susceptibility to secondary Candida infection. By contrast, changes in levels of CD86+-activated macrophages, and the proportion of the PD-1+ population among the CD86+ macrophages in CLP mice were found to be related to secondary fungal infection susceptibility. CONCLUSIONS: Macrophage activation and exhaustion might be a significant determinant in susceptibility to fungal infection, and outcomes of infection. This study provided more comprehensive knowledge pertinent to patient evaluation and therapeutics design in restoring host defenses against secondary fungal infection in those with sepsis.
BACKGROUND: Secondary fungal infection is a major complication in patients with sepsis-associated immunosuppression. However, sepsis-induced immune alterations related to fungal susceptibility have not been well characterized. OBJECTIVES: To determine kinetic changes in the immune phenotype by determining the proportion of T cells, B cells and macrophages, and especially the expression of an immune exhaustion marker PD-1, in murine sepsis. In addition, sepsis -induced alterations of these immune cells were assessed in relation to susceptibility to secondary fungal infection. METHODS: Cecal ligation and puncture (CLP) was used as a mouse sepsis model, with Candida albicans as the secondary systemic fungal infection. Splenic T cells, B cells and macrophages were assessed by flow cytometry. RESULTS: Alterations in T cell and B cell numbers and the proportion of PD-1 expressing T cells and B cells in CLP mice were not clearly related to susceptibility to secondary Candida infection. By contrast, changes in levels of CD86+-activated macrophages, and the proportion of the PD-1+ population among the CD86+ macrophages in CLP mice were found to be related to secondary fungal infection susceptibility. CONCLUSIONS: Macrophage activation and exhaustion might be a significant determinant in susceptibility to fungal infection, and outcomes of infection. This study provided more comprehensive knowledge pertinent to patient evaluation and therapeutics design in restoring host defenses against secondary fungal infection in those with sepsis.