Host response to influenza infections in human blood: association of influenza severity with host genetics and transcriptomic response.

Autor:	Schughart K; Institute of Virology Münster, University of Münster, Münster, Germany.; Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, TN, United States., Smith AM; Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, TN, United States.; Department of Pediatrics, University of Tennessee Health Science Center, Memphis, TN, United States., Tsalik EL; Division of Infectious Diseases, Department of Medicine, Duke University School of Medicine, Durham, NC, United States., Threlkeld SC; Baptist Memorial Hospital, Memphis, TN, United States., Sellers S; Division of Pulmonary Diseases and Critical Care Medicine, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States., Fischer WA 2nd; Division of Pulmonary Diseases and Critical Care Medicine, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States., Schreiber J; Clinic of Pneumology, Otto-von-Guerike University, Magdeburg, Germany., Lücke E; Clinic of Pneumology, Otto-von-Guerike University, Magdeburg, Germany., Cornberg M; Centre for Individualised Infection Medicine (CiiM), a Joint Initiative of the Helmholtz Centre for Infection Research (HZI) and Hannover Medical School (MHH), Hannover, Germany.; Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, Hannover Medical School (MHH), Hannover, Germany.; German Centre for Infection Research (DZIF), Partner Site Hannover-Braunschweig, Hannover, Germany.; TWINCORE Centre for Experimental and Clinical Infection Research, a Joint Venture Between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany., Debarry J; Centre for Individualised Infection Medicine (CiiM), a Joint Initiative of the Helmholtz Centre for Infection Research (HZI) and Hannover Medical School (MHH), Hannover, Germany.; TWINCORE Centre for Experimental and Clinical Infection Research, a Joint Venture Between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany., Woods CW; Division of Infectious Diseases, Department of Medicine, Duke University School of Medicine, Durham, NC, United States.; Center for Infectious Disease Diagnostics and Innovation, Department of Medicine, Duke University School of Medicine, Durham, NC, United States., McClain MT; Division of Infectious Diseases, Department of Medicine, Duke University School of Medicine, Durham, NC, United States.; Center for Infectious Disease Diagnostics and Innovation, Department of Medicine, Duke University School of Medicine, Durham, NC, United States., Heise M; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2024 Aug 13; Vol. 15, pp. 1385362. Date of Electronic Publication: 2024 Aug 13 (Print Publication: 2024).
DOI:	10.3389/fimmu.2024.1385362
Abstrakt:	Introduction: Influenza virus infections are a major global health problem. Influenza can result in mild/moderate disease or progress to more severe disease, leading to high morbidity and mortality. Severity is thought to be primarily driven by immunopathology, but predicting which individuals are at a higher risk of being hospitalized warrants investigation into host genetics and the molecular signatures of the host response during influenza infections. Methods: Here, we performed transcriptome and genotype analysis in healthy controls and patients exhibiting mild/moderate or severe influenza (ICU patients). A unique aspect of our study was the genotyping of all participants, which allowed us to assign ethnicities based on genetic variation and assess whether the variation was correlated with expression levels. Results: We identified 169 differentially expressed genes and related molecular pathways between patients in the ICU and those who were not in the ICU. The transcriptome/genotype association analysis identified 871 genes associated to a genetic variant and 39 genes distinct between African-Americans and Caucasians. We also investigated the effects of age and sex and found only a few discernible gene effects in our cohort. Discussion: Together, our results highlight select risk factors that may contribute to an increased risk of ICU admission for influenza-infected patients. This should help to develop better diagnostic tools based on molecular signatures, in addition to a better understanding of the biological processes in the host response to influenza. Competing Interests: During the conduct of this study, ET and CW were co-founders of Predigen, Inc. and held equity in Biomeme, Inc. ET is currently employed by and holds equity in Danaher Corp. ET and CW have patents pending or granted for Methods to Diagnose and Treat Acute Respiratory Infections; Gene Expression Signatures Useful to Predict or Diagnose Sepsis and Methods of Using the Same; Methods for Characterizing Infections and Methods for Developing Tests for the Same; and Systems and methods for determining status, type, severity, and/or risk of infection. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest. (Copyright © 2024 Schughart, Smith, Tsalik, Threlkeld, Sellers, Fischer, Schreiber, Lücke, Cornberg, Debarry, Woods, McClain and Heise.)
Databáze:	MEDLINE
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