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Published on: September 19, 2025
CD14 plays a limited role during influenza A virus infection in vivo
Mark C Dessing1, Koenraad F van der Sluijs, Sandrine Florquin
1Center of Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands. m.c.dessing@amc.uva.nl
Abstract:
Influenza A is a single stranded (ss)RNA virus that can cause upper respiratory tract infections that in rare cases may progress to pneumonia. Toll-like receptors (TLRs) and CD14 are receptors which recognize viral proteins and nucleic acid of several viruses. CD14 is required for influenza-induced cytokine production during infection of mouse macrophages. In addition, CD14 was shown to bind ssRNA, suggesting an important role for CD14 during infection with influenza. To investigate the role of CD14 during influenza pneumonia we inoculated WT and CD14 KO mice with a non-lethal dose of a mouse adapted strain of influenza A. CD14 KO mice displayed a reduced viral load in the lungs, 2 and 14 days after infection with influenza. Pulmonary cytokine production in CD14 KO mice was reduced at day 2 and elevated at day 8 compared to WT mice. CD14 deficiency did not influence lymphocyte recruitment or lymphocyte activation in lungs and draining lymph nodes 8 days after infection. These data show that CD14 plays a limited role in host defense against infection with influenza.
Insights
Toll-like receptors (TLRs) and CD14 are key in recognizing viral invaders. CD14 plays a limited role in host defense against influenza A, impacting viral load and cytokine production but not lymphocyte responses.
Area of Science:
- Immunology
- Virology
- Respiratory Medicine
Background:
- Influenza A is an ssRNA virus causing respiratory infections, potentially leading to pneumonia.
- Toll-like receptors (TLRs) and CD14 are crucial for recognizing viral components.
- CD14's role in binding ssRNA suggests involvement in influenza infections.
Purpose of the Study:
- To investigate the specific role of CD14 in the host defense against influenza A pneumonia.
- To determine the impact of CD14 deficiency on viral load, cytokine production, and immune cell responses.
Main Methods:
- Wild-type (WT) and CD14 knockout (KO) mice were infected with a non-lethal dose of influenza A.
- Viral load in the lungs was assessed at 2 and 14 days post-infection.
- Pulmonary cytokine levels and lymphocyte recruitment/activation were analyzed at specific time points.
Main Results:
- CD14 KO mice exhibited reduced viral load in the lungs at 2 and 14 days post-infection.
- Pulmonary cytokine production differed between CD14 KO and WT mice (reduced at day 2, elevated at day 8).
- Lymphocyte recruitment and activation in lungs and lymph nodes were not significantly influenced by CD14 deficiency.
Conclusions:
- CD14 plays a limited role in the overall host defense mechanisms against influenza A infection.
- While CD14 affects viral clearance and initial cytokine responses, it does not critically impact adaptive immune cell functions in this model.
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