tetano
Editor, Senior Moderator
J Clin Invest
. 2024 Sep 10:e180986.
doi: 10.1172/JCI180986. Online ahead of print. Antibiotic use during influenza infection augments lung eosinophils that impair immunity against secondary bacterial pneumonia
Marilia Sanches Santos Rizzo Zuttion[SUP] 1 [/SUP], Tanyalak Parimon[SUP] 1 [/SUP], Stephanie A Bora[SUP] 1 [/SUP], Changfu Yao[SUP] 1 [/SUP], Katherine Lagree[SUP] 2 [/SUP], Catherine A Gao[SUP] 3 [/SUP], Richard G Wunderink[SUP] 3 [/SUP], Georgios D Kitsios[SUP] 4 [/SUP], Alison Morris[SUP] 4 [/SUP], Yingze Zhang[SUP] 4 [/SUP], Bryan J McVerry[SUP] 4 [/SUP], Matthew E Modes[SUP] 1 [/SUP], Alberto M Marchevsky[SUP] 5 [/SUP], Barry R Stripp[SUP] 1 [/SUP], Christopher M Soto[SUP] 1 [/SUP], Ying Wang[SUP] 1 [/SUP], Kimberly Merene[SUP] 1 [/SUP], Silvia Cho[SUP] 1 [/SUP], Blandine L Victor[SUP] 1 [/SUP], Ivan Vujkovic-Cvijin[SUP] 1 [/SUP], Suman Gupta[SUP] 1 [/SUP], Suzanne Cassel[SUP] 1 [/SUP], Fayyaz S Sutterwala[SUP] 1 [/SUP], Suzanne Devkota[SUP] 1 [/SUP], David M Underhill[SUP] 2 [/SUP], Peter Chen[SUP] 6 [/SUP]
Affiliations
A leading cause of mortality after influenza infection is the development of a secondary bacterial pneumonia. In the absence of a bacterial superinfection, prescribing antibacterial therapies is not indicated but has become a common clinical practice for those presenting with a respiratory viral illness. In a murine model, we found that antibiotic use during influenza infection impaired the lung innate immunologic defenses toward a secondary challenge with methicillin-resistant Staphylococcus aureus (MRSA). Antibiotics augment lung eosinophils, which have inhibitory effects on macrophage function through the release of major basic protein. Moreover, we demonstrated antibiotic treatment during influenza infection causes a fungal dysbiosis that drive lung eosinophilia and impair MRSA clearance. Finally, we evaluated three cohorts of hospitalized patients and found eosinophils positively correlated with antibiotic use, systemic inflammation, and worsened outcomes. Altogether, our work demonstrates a detrimental effect of antibiotic treatment during influenza infection that has harmful immunologic consequences via recruitment of eosinophils to the lungs thereby increasing the risk of developing a secondary bacterial infection.
Keywords: Bacterial infections; Infectious disease; Influenza; Innate immunity; Pulmonology.
. 2024 Sep 10:e180986.
doi: 10.1172/JCI180986. Online ahead of print. Antibiotic use during influenza infection augments lung eosinophils that impair immunity against secondary bacterial pneumonia
Marilia Sanches Santos Rizzo Zuttion[SUP] 1 [/SUP], Tanyalak Parimon[SUP] 1 [/SUP], Stephanie A Bora[SUP] 1 [/SUP], Changfu Yao[SUP] 1 [/SUP], Katherine Lagree[SUP] 2 [/SUP], Catherine A Gao[SUP] 3 [/SUP], Richard G Wunderink[SUP] 3 [/SUP], Georgios D Kitsios[SUP] 4 [/SUP], Alison Morris[SUP] 4 [/SUP], Yingze Zhang[SUP] 4 [/SUP], Bryan J McVerry[SUP] 4 [/SUP], Matthew E Modes[SUP] 1 [/SUP], Alberto M Marchevsky[SUP] 5 [/SUP], Barry R Stripp[SUP] 1 [/SUP], Christopher M Soto[SUP] 1 [/SUP], Ying Wang[SUP] 1 [/SUP], Kimberly Merene[SUP] 1 [/SUP], Silvia Cho[SUP] 1 [/SUP], Blandine L Victor[SUP] 1 [/SUP], Ivan Vujkovic-Cvijin[SUP] 1 [/SUP], Suman Gupta[SUP] 1 [/SUP], Suzanne Cassel[SUP] 1 [/SUP], Fayyaz S Sutterwala[SUP] 1 [/SUP], Suzanne Devkota[SUP] 1 [/SUP], David M Underhill[SUP] 2 [/SUP], Peter Chen[SUP] 6 [/SUP]
Affiliations
- PMID: 39255040
- DOI: 10.1172/JCI180986
A leading cause of mortality after influenza infection is the development of a secondary bacterial pneumonia. In the absence of a bacterial superinfection, prescribing antibacterial therapies is not indicated but has become a common clinical practice for those presenting with a respiratory viral illness. In a murine model, we found that antibiotic use during influenza infection impaired the lung innate immunologic defenses toward a secondary challenge with methicillin-resistant Staphylococcus aureus (MRSA). Antibiotics augment lung eosinophils, which have inhibitory effects on macrophage function through the release of major basic protein. Moreover, we demonstrated antibiotic treatment during influenza infection causes a fungal dysbiosis that drive lung eosinophilia and impair MRSA clearance. Finally, we evaluated three cohorts of hospitalized patients and found eosinophils positively correlated with antibiotic use, systemic inflammation, and worsened outcomes. Altogether, our work demonstrates a detrimental effect of antibiotic treatment during influenza infection that has harmful immunologic consequences via recruitment of eosinophils to the lungs thereby increasing the risk of developing a secondary bacterial infection.
Keywords: Bacterial infections; Infectious disease; Influenza; Innate immunity; Pulmonology.