Influenza virus-induced glucocorticoids compromise innate host defense against a secondary bacterial infection.
Multicellular organisms are continuously exposed to many different pathogens. Because different classes of pathogens require different types of immune responses, understanding how an ongoing immune response to one type of infection affects the host's ability to respond to another pathogen is essential for a complete understanding of host-pathogen interactions. Here, we used a mouse model of coinfection to gain insight into the effect of respiratory influenza virus infection on a subsequent systemic bacterial infection. We found that influenza infection triggered a generalized stress response leading to a sustained increase in serum glucocorticoid levels, resulting in a systemic suppression of immune responses. However, virus-induced glucocorticoid production was necessary to control the inflammatory response and prevent lethal immunopathology during coinfection. This study demonstrates that activation of the hypothalamic-pituitary-adrenal axis controls the balance between immune defense and immunopathology and is an important component of the host response to coinfection.
Jamieson
Amanda M
AM
Howard Hughes Medical Institute and Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06510, USA.
Yu
Shuang
S
Annicelli
Charles H
CH
Medzhitov
Ruslan
R
D000418:Albumins / Q000032:analysis; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D015169:Colony Count, Microbial; D016207:Cytokines / Q000032:analysis; D005938:Glucocorticoids / Q000097:blood / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance; D007113:Immunity, Innate; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D008089:Listeria monocytogenes / Q000302:isolation & purification; D008088:Listeriosis / Q000276:immunology*; D008099:Liver / Q000382:microbiology; D008168:Lung / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections / Q000150:complications* / Q000276:immunology* / Q000473:pathology; D013154:Spleen / Q000382:microbiology; D016019:Survival Analysis; D019562:Viral Load
D000418:Albumins; D016207:Cytokines; D005938:Glucocorticoids