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Human coagulation factor X-adenovirus type 5 complexes poorly stimulate an innate immune response in human
Karsten Eichholz1, Franck J D Mennechet1, Eric J Kremer2
1Institut de Génétique Moléculaire de Montpellier, Montpellier, France Université de Montpellier, Montpellier, France.
Unlabelled:
One of the first lines of host defense against many viruses in vertebrates is the innate immune system, which detects pathogen-associated molecular patterns (PAMPs) using pathogen recognition receptors (PRR). The dynamic interactions between pathogens and hosts create, in some cases, species-specific relationships. Recently, it was shown that murine factor X (mFX)-armored human adenovirus (HAd) stimulated a mFX-Toll-like receptor 4 (TLR4)-associated response in mouse macrophages in vitro and in vivo. Given the importance of studies using animals to better understand host-pathogen interactions, we asked if human FX (hFX)-armored HAd type 5 (HAd5) was capable of activating innate immune sensors in primary human mononuclear phagocytes. To this end, we assayed human mononuclear phagocytes for their ability to be stimulated by hFX-armored HAd5 via a TLR/NF-κB pathway, in particular, a TLR4 pathway. In our hands, we found no significant interaction, activation, or maturation of human mononuclear phagocytes caused by the presence of hFX-armored HAd5.
Importance:
Animals, and mice in particular, are often used as informative and powerful surrogates for how pathogens interact with natural host systems. When possible, extended and targeted studies in the natural host can then be performed. Our data will help us understand the differences in preclinical testing in mice and clinical use in humans in order to improve treatment for HAd diseases and Ad vector effectiveness.
Insights
Human adenovirus (HAd) armored with human factor X (hFX) did not activate innate immune sensors in human cells, unlike its mouse counterpart. This suggests species-specific differences in host-pathogen interactions are crucial for adenovirus research.
Area of Science:
- Immunology
- Virology
- Infectious Diseases
Background:
- The innate immune system, utilizing pathogen recognition receptors (PRRs), is a primary defense against viral infections.
- Murine factor X (mFX)-armored human adenovirus (HAd) activates Toll-like receptor 4 (TLR4) in mouse immune cells.
- Understanding host-pathogen interactions is vital for developing effective antiviral therapies and improving adenovirus vector efficacy.
Purpose of the Study:
- To investigate if human factor X (hFX)-armored HAd type 5 (HAd5) activates innate immune sensors in human mononuclear phagocytes.
- To determine if hFX-armored HAd5 triggers a Toll-like receptor (TLR)/NF-κB pathway, specifically TLR4, in human cells.
- To identify species-specific differences in immune responses to factor X-armored adenoviruses.
Main Methods:
- Primary human mononuclear phagocytes were isolated and cultured.
- Cells were exposed to hFX-armored HAd5.
- Immune cell activation, maturation, and TLR/NF-κB pathway signaling were assayed.
Main Results:
- hFX-armored HAd5 did not induce significant interaction with human mononuclear phagocytes.
- No activation or maturation of human mononuclear phagocytes was observed upon exposure to hFX-armored HAd5.
- The TLR4-associated pathway was not significantly stimulated by hFX-armored HAd5 in human cells.
Conclusions:
- hFX-armored HAd5 does not activate innate immune sensors in human mononuclear phagocytes via the TLR4 pathway.
- This finding highlights species-specific differences in the innate immune response to factor X-armored adenoviruses.
- Results emphasize the importance of studying host-pathogen interactions in the natural host species for accurate preclinical testing and clinical application.
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