Immunomodulation Induced During Interferon-α Therapy Impairs the Anti-HBV Immune Response Through CD24CD38 B Cells

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2021 Jan 11

PMID 33424840

Citations 8

Authors

Binqing Fu

Dongyao Wang

Xiaokun Shen

Chuang Guo

Yanyan Liu

Ying Ye

Rui Sun

Jiabin Li

Zhigang Tian

Haiming Wei

Affiliations

Soon will be listed here.

Abstract

Type I interferon is widely used for antiviral therapy, yet has yielded disappointing results toward chronic HBV infection. Here we identify that PEG-IFNα-2b therapy toward persistent infection in humans is a double-edged sword of both immunostimulation and immunomodulation. Our studies of this randomised trial showed persistent PEG-IFNα-2b therapy induced large number of CD24CD38 B cells and launched a CD24CD38 B cells centered immunosuppressive response, including downregulating functions of T cells and NK cells. Patients with low induced CD24CD38 B cells have achieved an improved therapeutic effect. Specifically, using the anti-CD24 antibody to deplete CD24CD38 B cells without harming other B cell subsets suggest a promising strategy to improve the therapeutic effects. Our findings show that PEG-IFNα-2b therapy toward persistent infection constitutes an immunomodulation effect, and strategies to identifying the molecular basis for the antiviral versus immunomodulatory effects of PEG-IFNα-2b to selectively manipulate these opposing activities provide an opportunity to ameliorate anti-virus immunity and control viral infection.

Citing Articles

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References

Schweitzer A, Horn J, Mikolajczyk R, Krause G, Ott J . Estimations of worldwide prevalence of chronic hepatitis B virus infection: a systematic review of data published between 1965 and 2013. Lancet. 2015; 386(10003):1546-55. DOI: 10.1016/S0140-6736(15)61412-X. View

Tang X, Zhang S, Peng Q, Ling L, Shi H, Liu Y . Sustained IFN-I stimulation impairs MAIT cell responses to bacteria by inducing IL-10 during chronic HIV-1 infection. Sci Adv. 2020; 6(8):eaaz0374. PMC: 7030930. DOI: 10.1126/sciadv.aaz0374. View

Sarvaria A, Madrigal J, Saudemont A . B cell regulation in cancer and anti-tumor immunity. Cell Mol Immunol. 2017; 14(8):662-674. PMC: 5549607. DOI: 10.1038/cmi.2017.35. View

Aspord C, Bruder Costa J, Jacob M, Dufeu-Duchesne T, Bertucci I, Pouget N . Remodeling of B-Cell Subsets in Blood during Pegylated IFNα-2a Therapy in Patients with Chronic Hepatitis B Infection. PLoS One. 2016; 11(6):e0156200. PMC: 4900671. DOI: 10.1371/journal.pone.0156200. View

Barkal A, Brewer R, Markovic M, Kowarsky M, Barkal S, Zaro B . CD24 signalling through macrophage Siglec-10 is a target for cancer immunotherapy. Nature. 2019; 572(7769):392-396. PMC: 6697206. DOI: 10.1038/s41586-019-1456-0. View

Thimme R, Dandri M . Dissecting the divergent effects of interferon-alpha on immune cells: time to rethink combination therapy in chronic hepatitis B?. J Hepatol. 2012; 58(2):205-9. DOI: 10.1016/j.jhep.2012.11.007. View

Rosser E, Blair P, Mauri C . Cellular targets of regulatory B cell-mediated suppression. Mol Immunol. 2014; 62(2):296-304. DOI: 10.1016/j.molimm.2014.01.014. View

Flores-Borja F, Bosma A, Ng D, Reddy V, Ehrenstein M, Isenberg D . CD19+CD24hiCD38hi B cells maintain regulatory T cells while limiting TH1 and TH17 differentiation. Sci Transl Med. 2013; 5(173):173ra23. DOI: 10.1126/scitranslmed.3005407. View

Kleinmanns K, Fosse V, Davidson B, Garcia de Jalon E, Tenstad O, Bjorge L . CD24-targeted intraoperative fluorescence image-guided surgery leads to improved cytoreduction of ovarian cancer in a preclinical orthotopic surgical model. EBioMedicine. 2020; 56:102783. PMC: 7248677. DOI: 10.1016/j.ebiom.2020.102783. View

10.

Saidova A, Bublin M, Schmidthaler K, Fajgelj V, Klinglmueller F, Spittler A . Evidence for a Role of TGF-β-Activated Kinase 1 and MAP3K7 Binding Protein 3 in Peanut-Specific T-Cell Responses. Int Arch Allergy Immunol. 2019; 179(1):10-16. DOI: 10.1159/000496438. View

11.

Ni Y, Zhao X, Wang W . CD24, A Review of its Role in Tumor Diagnosis, Progression and Therapy. Curr Gene Ther. 2020; 20(2):109-126. DOI: 10.2174/1566523220666200623170738. View

12.

Mauri C, Bosma A . Immune regulatory function of B cells. Annu Rev Immunol. 2012; 30:221-41. DOI: 10.1146/annurev-immunol-020711-074934. View

13.

Menon M, Blair P, Isenberg D, Mauri C . A Regulatory Feedback between Plasmacytoid Dendritic Cells and Regulatory B Cells Is Aberrant in Systemic Lupus Erythematosus. Immunity. 2016; 44(3):683-697. PMC: 4803914. DOI: 10.1016/j.immuni.2016.02.012. View

14.

Auerbuch V, Brockstedt D, Meyer-Morse N, ORiordan M, Portnoy D . Mice lacking the type I interferon receptor are resistant to Listeria monocytogenes. J Exp Med. 2004; 200(4):527-33. PMC: 2211930. DOI: 10.1084/jem.20040976. View

15.

Teijaro J, Ng C, Lee A, Sullivan B, Sheehan K, Welch M . Persistent LCMV infection is controlled by blockade of type I interferon signaling. Science. 2013; 340(6129):207-11. PMC: 3640797. DOI: 10.1126/science.1235214. View

16.

Maude S, Frey N, Shaw P, Aplenc R, Barrett D, Bunin N . Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med. 2014; 371(16):1507-17. PMC: 4267531. DOI: 10.1056/NEJMoa1407222. View

17.

Wilson E, Yamada D, Elsaesser H, Herskovitz J, Deng J, Cheng G . Blockade of chronic type I interferon signaling to control persistent LCMV infection. Science. 2013; 340(6129):202-7. PMC: 3704950. DOI: 10.1126/science.1235208. View

18.

Sandler N, Bosinger S, Estes J, Zhu R, Tharp G, Boritz E . Type I interferon responses in rhesus macaques prevent SIV infection and slow disease progression. Nature. 2014; 511(7511):601-5. PMC: 4418221. DOI: 10.1038/nature13554. View

19.

Blair P, Norena L, Flores-Borja F, Rawlings D, Isenberg D, Ehrenstein M . CD19(+)CD24(hi)CD38(hi) B cells exhibit regulatory capacity in healthy individuals but are functionally impaired in systemic Lupus Erythematosus patients. Immunity. 2010; 32(1):129-40. DOI: 10.1016/j.immuni.2009.11.009. View

20.

Mayer-Barber K, Yan B . Clash of the Cytokine Titans: counter-regulation of interleukin-1 and type I interferon-mediated inflammatory responses. Cell Mol Immunol. 2016; 14(1):22-35. PMC: 5214938. DOI: 10.1038/cmi.2016.25. View