Skewed CD39/CD73/adenosine pathway in B cells is associated with innate immune hyperactivation in chronic HIV-1 infection
Abstract Background The CD39/CD73/adenosine suppression pathway correlates with disease progression in patients with chronic human immunodeficiency virus 1 (HIV-1) infection; however, the relationships between this pathway in B cells and innate immune hyperactivation remain largely undefined. Method...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-02-01
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| Series: | Translational Medicine Communications |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s41231-019-0033-8 |
| _version_ | 1819151704445157376 |
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| author | Wen-Xian Chang Hui-Huang Huang Lei Huang Ji-Jing Shi Yan-Mei Jiao Chao Zhang Lei Jin Tao Yang Ming Shi Bo Tu Zhe Xu Tian-Jun Jiang Fu-Sheng Wang Ji-Yuan Zhang |
| author_facet | Wen-Xian Chang Hui-Huang Huang Lei Huang Ji-Jing Shi Yan-Mei Jiao Chao Zhang Lei Jin Tao Yang Ming Shi Bo Tu Zhe Xu Tian-Jun Jiang Fu-Sheng Wang Ji-Yuan Zhang |
| author_sort | Wen-Xian Chang |
| collection | DOAJ |
| description | Abstract Background The CD39/CD73/adenosine suppression pathway correlates with disease progression in patients with chronic human immunodeficiency virus 1 (HIV-1) infection; however, the relationships between this pathway in B cells and innate immune hyperactivation remain largely undefined. Methods In this study, we examined CD39 and CD73 expression, and adenosine production by B cells from 136 patients with chronic HIV-1 infection. Results The CD39 and CD73 expression levels on total B cells (and their subsets) decreased continuously in typical progressors (TPs), but were gradually recovered in complete responders. In TPs, the frequencies of CD39+, CD73+, and CD39+CD73+ B cells inversely correlated with HIV-1 viral load and positively correlated with CD4 T cell counts, but also positively associated with CD4/CD8 ratioes and inversely correlated with markers for intestinal epithelial injury and microbial translocation. Furthermore, B cells from TPs showed a markedly reduced capacity to generate CD39/CD73-dependent extracellular adenosine; the loss of this capacity was more serious in patients with acquired immunodeficiency syndrome. In vitro, increased adenosine could inhibit the activation of monocytes and suppress the ability of monocytes and T cells to produce TNF-alpha, regardless of their infection status. Moreover, adenosine could inhibit activation-induced HIV-1 virion production and p24 expression. Conclusions These findings provided a new role of B cell pathology in HIV-1 infection, in which the skewed CD39/CD73/adenosine pathway in B cells linked to microbial translocation-induced innate immune hyperactivation, supporting the notion that regulating the adenosine pathway in B cells might be an attractive approach to treat patients with HIV-1-infection. |
| first_indexed | 2024-12-22T14:37:38Z |
| format | Article |
| id | doaj.art-0c217a27a98e4a26a3e1188dc3fa8150 |
| institution | Directory Open Access Journal |
| issn | 2396-832X |
| language | English |
| last_indexed | 2024-12-22T14:37:38Z |
| publishDate | 2019-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Translational Medicine Communications |
| spelling | doaj.art-0c217a27a98e4a26a3e1188dc3fa81502022-12-21T18:22:37ZengBMCTranslational Medicine Communications2396-832X2019-02-014111110.1186/s41231-019-0033-8Skewed CD39/CD73/adenosine pathway in B cells is associated with innate immune hyperactivation in chronic HIV-1 infectionWen-Xian Chang0Hui-Huang Huang1Lei Huang2Ji-Jing Shi3Yan-Mei Jiao4Chao Zhang5Lei Jin6Tao Yang7Ming Shi8Bo Tu9Zhe Xu10Tian-Jun Jiang11Fu-Sheng Wang12Ji-Yuan Zhang13Treatment and Research Center for Infectious Diseases, The fifth Medical Center of PLA General Hospital, Beijing 302 HospitalTreatment and Research Center for Infectious Diseases, The fifth Medical Center of PLA General Hospital, Beijing 302 HospitalTreatment and Research Center for Infectious Diseases, The fifth Medical Center of PLA General Hospital, Beijing 302 HospitalThe First People’s Hospital of ZhengzhouTreatment and Research Center for Infectious Diseases, The fifth Medical Center of PLA General Hospital, Beijing 302 HospitalTreatment and Research Center for Infectious Diseases, The fifth Medical Center of PLA General Hospital, Beijing 302 HospitalTreatment and Research Center for Infectious Diseases, The fifth Medical Center of PLA General Hospital, Beijing 302 HospitalTreatment and Research Center for Infectious Diseases, The fifth Medical Center of PLA General Hospital, Beijing 302 HospitalTreatment and Research Center for Infectious Diseases, The fifth Medical Center of PLA General Hospital, Beijing 302 HospitalTreatment and Research Center for Infectious Diseases, The fifth Medical Center of PLA General Hospital, Beijing 302 HospitalTreatment and Research Center for Infectious Diseases, The fifth Medical Center of PLA General Hospital, Beijing 302 HospitalTreatment and Research Center for Infectious Diseases, The fifth Medical Center of PLA General Hospital, Beijing 302 HospitalTreatment and Research Center for Infectious Diseases, The fifth Medical Center of PLA General Hospital, Beijing 302 HospitalTreatment and Research Center for Infectious Diseases, The fifth Medical Center of PLA General Hospital, Beijing 302 HospitalAbstract Background The CD39/CD73/adenosine suppression pathway correlates with disease progression in patients with chronic human immunodeficiency virus 1 (HIV-1) infection; however, the relationships between this pathway in B cells and innate immune hyperactivation remain largely undefined. Methods In this study, we examined CD39 and CD73 expression, and adenosine production by B cells from 136 patients with chronic HIV-1 infection. Results The CD39 and CD73 expression levels on total B cells (and their subsets) decreased continuously in typical progressors (TPs), but were gradually recovered in complete responders. In TPs, the frequencies of CD39+, CD73+, and CD39+CD73+ B cells inversely correlated with HIV-1 viral load and positively correlated with CD4 T cell counts, but also positively associated with CD4/CD8 ratioes and inversely correlated with markers for intestinal epithelial injury and microbial translocation. Furthermore, B cells from TPs showed a markedly reduced capacity to generate CD39/CD73-dependent extracellular adenosine; the loss of this capacity was more serious in patients with acquired immunodeficiency syndrome. In vitro, increased adenosine could inhibit the activation of monocytes and suppress the ability of monocytes and T cells to produce TNF-alpha, regardless of their infection status. Moreover, adenosine could inhibit activation-induced HIV-1 virion production and p24 expression. Conclusions These findings provided a new role of B cell pathology in HIV-1 infection, in which the skewed CD39/CD73/adenosine pathway in B cells linked to microbial translocation-induced innate immune hyperactivation, supporting the notion that regulating the adenosine pathway in B cells might be an attractive approach to treat patients with HIV-1-infection.http://link.springer.com/article/10.1186/s41231-019-0033-8Human immunodeficiency virus 1B cellCD39CD73Immune hyperactivation |
| spellingShingle | Wen-Xian Chang Hui-Huang Huang Lei Huang Ji-Jing Shi Yan-Mei Jiao Chao Zhang Lei Jin Tao Yang Ming Shi Bo Tu Zhe Xu Tian-Jun Jiang Fu-Sheng Wang Ji-Yuan Zhang Skewed CD39/CD73/adenosine pathway in B cells is associated with innate immune hyperactivation in chronic HIV-1 infection Translational Medicine Communications Human immunodeficiency virus 1 B cell CD39 CD73 Immune hyperactivation |
| title | Skewed CD39/CD73/adenosine pathway in B cells is associated with innate immune hyperactivation in chronic HIV-1 infection |
| title_full | Skewed CD39/CD73/adenosine pathway in B cells is associated with innate immune hyperactivation in chronic HIV-1 infection |
| title_fullStr | Skewed CD39/CD73/adenosine pathway in B cells is associated with innate immune hyperactivation in chronic HIV-1 infection |
| title_full_unstemmed | Skewed CD39/CD73/adenosine pathway in B cells is associated with innate immune hyperactivation in chronic HIV-1 infection |
| title_short | Skewed CD39/CD73/adenosine pathway in B cells is associated with innate immune hyperactivation in chronic HIV-1 infection |
| title_sort | skewed cd39 cd73 adenosine pathway in b cells is associated with innate immune hyperactivation in chronic hiv 1 infection |
| topic | Human immunodeficiency virus 1 B cell CD39 CD73 Immune hyperactivation |
| url | http://link.springer.com/article/10.1186/s41231-019-0033-8 |
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