CD14 Is Involved in the Interferon Response of Human Macrophages to Rubella Virus Infection

Overview

Journal Biomedicines

Specialty Biomedical Engineering

Date 2022 Feb 25

PMID 35203475

Authors

Erik Schilling

Lukas Pfeiffer

Sunna Hauschildt

Ulrike Koehl

Claudia Claus

Affiliations

Soon will be listed here.

Abstract

Macrophages (MΦ) as specialized immune cells are involved in rubella virus (RuV) pathogenesis and enable the study of its interaction with the innate immune system. A similar replication kinetics of RuV in the two human MΦ types, the pro-inflammatory M1-like (or GM-MΦ) and anti-inflammatory M2-like (M-MΦ), was especially in M-MΦ accompanied by a reduction in the expression of the innate immune receptor CD14. Similar to RuV infection, exogenous interferon (IFN) β induced a loss of glycolytic reserve in M-MΦ, but in contrast to RuV no noticeable influence on CD14 expression was detected. We next tested the contribution of CD14 to the generation of cytokines/chemokines during RuV infection of M-MΦ through the application of anti-CD14 blocking antibodies. Blockage of CD14 prior to RuV infection enhanced generation of virus progeny. In agreement with this observation, the expression of IFNs was significantly reduced in comparison to the isotype control. Additionally, the expression of TNF-α was slightly reduced, whereas the chemokine CXCL10 was not altered. In conclusion, the observed downmodulation of CD14 during RuV infection of M-MΦ appears to contribute to virus-host-adaptation through a reduction of the IFN response.

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References

Rouse B, Horohov D . Immunosuppression in viral infections. Rev Infect Dis. 1986; 8(6):850-73. PMC: 7792945. DOI: 10.1093/clinids/8.6.850. View

Perelygina L, Plotkin S, Russo P, Hautala T, Bonilla F, Ochs H . Rubella persistence in epidermal keratinocytes and granuloma M2 macrophages in patients with primary immunodeficiencies. J Allergy Clin Immunol. 2016; 138(5):1436-1439.e11. PMC: 5392721. DOI: 10.1016/j.jaci.2016.06.030. View

Wu Z, Zhang Z, Lei Z, Lei P . CD14: Biology and role in the pathogenesis of disease. Cytokine Growth Factor Rev. 2019; 48:24-31. DOI: 10.1016/j.cytogfr.2019.06.003. View

Jimenez-Duran G, Luque-Martin R, Patel M, Koppe E, Bernard S, Sharp C . Pharmacological validation of targets regulating CD14 during macrophage differentiation. EBioMedicine. 2020; 61:103039. PMC: 7648121. DOI: 10.1016/j.ebiom.2020.103039. View

Ovsyannikova I, Salk H, Larrabee B, Pankratz V, Poland G . Single nucleotide polymorphisms/haplotypes associated with multiple rubella-specific immune response outcomes post-MMR immunization in healthy children. Immunogenetics. 2015; 67(10):547-61. PMC: 4587390. DOI: 10.1007/s00251-015-0864-z. View

Schilling E, Grahnert A, Pfeiffer L, Koehl U, Claus C, Hauschildt S . The Impact of Rubella Virus Infection on a Secondary Inflammatory Response in Polarized Human Macrophages. Front Immunol. 2022; 12:772595. PMC: 8716696. DOI: 10.3389/fimmu.2021.772595. View

Rajaiah R, Perkins D, Ireland D, Vogel S . CD14 dependence of TLR4 endocytosis and TRIF signaling displays ligand specificity and is dissociable in endotoxin tolerance. Proc Natl Acad Sci U S A. 2015; 112(27):8391-6. PMC: 4500272. DOI: 10.1073/pnas.1424980112. View

Vidyarthi A, Khan N, Agnihotri T, Negi S, Das D, Aqdas M . TLR-3 Stimulation Skews M2 Macrophages to M1 Through IFN-αβ Signaling and Restricts Tumor Progression. Front Immunol. 2018; 9:1650. PMC: 6060442. DOI: 10.3389/fimmu.2018.01650. View

Yano S, Banno T, Walsh R, Blumenberg M . Transcriptional responses of human epidermal keratinocytes to cytokine interleukin-1. J Cell Physiol. 2007; 214(1):1-13. DOI: 10.1002/jcp.21300. View

10.

Dunne A, ONeill L . Adaptor usage and Toll-like receptor signaling specificity. FEBS Lett. 2005; 579(15):3330-5. DOI: 10.1016/j.febslet.2005.04.024. View

11.

McCarthy K . Cell cultures useful for the study of rubella. Am J Dis Child. 1969; 118(1):78-82. DOI: 10.1001/archpedi.1969.02100040080013. View

12.

Grahnert A, Weiss R, Schilling E, Stanslowsky N, Sack U, Hauschildt S . CD14 Counterregulates Lipopolysacharide-Induced Tumor Necrosis Factor-α Production in a Macrophage Subset. J Innate Immun. 2019; 11(4):359-374. PMC: 6738177. DOI: 10.1159/000495528. View

13.

Yamamoto M, Sato S, Hemmi H, Hoshino K, Kaisho T, Sanjo H . Role of adaptor TRIF in the MyD88-independent toll-like receptor signaling pathway. Science. 2003; 301(5633):640-3. DOI: 10.1126/science.1087262. View

14.

Ayithan N, Bradfute S, Anthony S, Stuthman K, Dye J, Bavari S . Ebola virus-like particles stimulate type I interferons and proinflammatory cytokine expression through the toll-like receptor and interferon signaling pathways. J Interferon Cytokine Res. 2013; 34(2):79-89. PMC: 3924795. DOI: 10.1089/jir.2013.0035. View

15.

Lu Q, Darveau R, Samaranayake L, Wang C, Jin L . Differential modulation of human {beta}-defensins expression in human gingival epithelia by Porphyromonas gingivalis lipopolysaccharide with tetra- and penta-acylated lipid A structures. Innate Immun. 2009; 15(6):325-35. DOI: 10.1177/1753425909104899. View

16.

Zobel S, Lorenz M, Frascaroli G, Bohnke J, Bilz N, Stanifer M . Rubella Virus Strain-Associated Differences in the Induction of Oxidative Stress Are Independent of Their Interferon Activation. Viruses. 2018; 10(10). PMC: 6213305. DOI: 10.3390/v10100540. View

17.

Martin T, Wurfel M, Zanoni I, Ulevitch R . Targeting innate immunity by blocking CD14: Novel approach to control inflammation and organ dysfunction in COVID-19 illness. EBioMedicine. 2020; 57:102836. PMC: 7305752. DOI: 10.1016/j.ebiom.2020.102836. View

18.

Ovsyannikova I, Dhiman N, Haralambieva I, Vierkant R, OByrne M, Jacobson R . Rubella vaccine-induced cellular immunity: evidence of associations with polymorphisms in the Toll-like, vitamin A and D receptors, and innate immune response genes. Hum Genet. 2009; 127(2):207-21. PMC: 2809817. DOI: 10.1007/s00439-009-0763-1. View

19.

Muraille E, Leo O, Moser M . TH1/TH2 paradigm extended: macrophage polarization as an unappreciated pathogen-driven escape mechanism?. Front Immunol. 2014; 5:603. PMC: 4244692. DOI: 10.3389/fimmu.2014.00603. View

20.

Perelygina L, Chen M, Suppiah S, Adebayo A, Abernathy E, Dorsey M . Infectious vaccine-derived rubella viruses emerge, persist, and evolve in cutaneous granulomas of children with primary immunodeficiencies. PLoS Pathog. 2019; 15(10):e1008080. PMC: 6837625. DOI: 10.1371/journal.ppat.1008080. View