Retrovirology | |
Systemic inhibition of myeloid dendritic cells by circulating HLA class I molecules in HIV-1 infection | |
Xu G Yu2  Mathias Lichterfeld3  Florencia Pereyra2  Katherine Seiss2  Mary F Carrington2  Jerome Rogich2  Maha Al-Mozaini1  Jinghe Huang2  | |
[1] King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia;Ragon Institute of MGH, MIT and Harvard, Boston, MA, USA;Infectious Disease Division, Massachusetts General Hospital, Boston, MA, USA | |
关键词: Leukocyte Immunoglobulin Like Receptor (LILR); immunoregulation; HLA; dendritic cells; HIV-1; | |
Others : 1209346 DOI : 10.1186/1742-4690-9-11 |
|
received in 2011-10-14, accepted in 2012-01-30, 发布年份 2012 | |
【 摘 要 】
Background
HIV-1 infection is associated with profound dysfunction of myeloid dendritic cells, for reasons that remain ill-defined. Soluble HLA class I molecules can have important inhibitory effects on T cells and NK cells, but may also contribute to reduced functional properties of professional antigen-presenting cells. Here, we investigated the expression of soluble HLA class I isoforms during HIV-1 infection and assessed their functional impact on antigen-presenting characteristics of dendritic cells.
Results
Soluble HLA class I molecules were highly upregulated in progressive HIV-1 infection as determined by quantitative Western blots. This was associated with strong increases of intracellular expression of HLA class I isoforms in dendritic cells and monocytes. Using mixed lymphocyte reactions, we found that soluble HLA class I molecules effectively inhibited the antigen-presenting properties of dendritic cells, however, there was no significant influence of HLA class I molecules on the cytokine-secretion properties of these cells. The immunomodulatory effects of soluble HLA class I molecules were mediated by interactions with inhibitory myelomonocytic MHC class I receptors from the Leukocyte Immunoglobulin Like Receptor (LILR) family.
Conclusions
During progressive HIV-1 infection, soluble HLA class I molecules can contribute to systemic immune dysfunction by inhibiting the antigen-presenting properties of myeloid dendritic cells through interactions with inhibitory myelomonocytic HLA class I receptors.
【 授权许可】
2012 Huang et al; licensee BioMed Central Ltd.
【 预 览 】
Files | Size | Format | View |
---|---|---|---|
20150602095819628.pdf | 459KB | download | |
Figure 4. | 32KB | Image | download |
Figure 3. | 28KB | Image | download |
Figure 2. | 49KB | Image | download |
Figure 1. | 104KB | Image | download |
【 图 表 】
Figure 1.
Figure 2.
Figure 3.
Figure 4.
【 参考文献 】
- [1]Appay V, Sauce D: Immune activation and inflammation in HIV-1 infection: causes and consequences. J Pathol 2008, 214:231-241.
- [2]Schulze Zur Wiesch J, Thomssen A, Hartjen P, Toth I, Lehmann C, Meyer-Olson D, Colberg K, Frerk S, Babikir D, Schmiedel S, et al.: Comprehensive analysis of frequency and phenotype of T regulatory cells in HIV infection: CD39 expression of FoxP3+ T regulatory cells correlates with progressive disease. J Virol 2011, 85:1287-1297.
- [3]Trautmann L, Janbazian L, Chomont N, Said EA, Gimmig S, Bessette B, Boulassel MR, Delwart E, Sepulveda H, Balderas RS, et al.: Upregulation of PD-1 expression on HIV-specific CD8+ T cells leads to reversible immune dysfunction. Nat Med 2006, 12:1198-1202.
- [4]Kaufmann DE, Kavanagh DG, Pereyra F, Zaunders JJ, Mackey EW, Miura T, Palmer S, Brockman M, Rathod A, Piechocka-Trocha A, et al.: Upregulation of CTLA-4 by HIV-specific CD4+ T cells correlates with disease progression and defines a reversible immune dysfunction. Nat Immunol 2007, 8:1246-1254.
- [5]Vlad G, Piazza F, Colovai A, Cortesini R, Della Pietra F, Suciu-Foca N, Manavalan JS: Interleukin-10 induces the upregulation of the inhibitory receptor ILT4 in monocytes from HIV positive individuals. Hum Immunol 2003, 64:483-489.
- [6]Huang J, Burke PS, Cung TD, Pereyra F, Toth I, Walker BD, Borges L, Lichterfeld M, Yu XG: Leukocyte immunoglobulin-like receptors maintain unique antigen-presenting properties of circulating myeloid dendritic cells in HIV-1-infected elite controllers. J Virol 2010, 84:9463-9471.
- [7]Allison JP, Pellegrino MA, Ferrone S, Callahan GN, Reisfeld RA: Biologic and chemical characterization of HLA antigens in human serum. J Immunol 1977, 118:1004-1009.
- [8]Singh PB, Brown RE, Roser B: Class I transplantation antigens in solution in body fluids and in the urine. Individuality signals to the environment. J Exp Med 1988, 168:195-211.
- [9]Krangel MS: Secretion of HLA-A and -B antigens via an alternative RNA splicing pathway. J Exp Med 1986, 163:1173-1190.
- [10]Dobbe LM, Stam NJ, Neefjes JJ, Giphart MJ: Biochemical complexity of serum HLA class I molecules. Immunogenetics 1988, 27:203-210.
- [11]Contini P, Ghio M, Merlo A, Brenci S, Filaci G, Indiveri F, Puppo F: Soluble HLA class I/CD8 ligation triggers apoptosis in EBV-specific CD8+ cytotoxic T lymphocytes by Fas/Fas-ligand interaction. Hum Immunol 2000, 61:1347-1351.
- [12]Spaggiari GM, Contini P, Dondero A, Carosio R, Puppo F, Indiveri F, Zocchi MR, Poggi A: Soluble HLA class I induces NK cell apoptosis upon the engagement of killer-activating HLA class I receptors through FasL-Fas interaction. Blood 2002, 100:4098-4107.
- [13]Spaggiari GM, Contini P, Carosio R, Arvigo M, Ghio M, Oddone D, Dondero A, Zocchi MR, Puppo F, Indiveri F, Poggi A: Soluble HLA class I molecules induce natural killer cell apoptosis through the engagement of CD8: evidence for a negative regulation exerted by members of the inhibitory receptor superfamily. Blood 2002, 99:1706-1714.
- [14]Brown D, Trowsdale J, Allen R: The LILR family: modulators of innate and adaptive immune pathways in health and disease. Tissue Antigens 2004, 64:215-225.
- [15]Puppo F, Brenci S, Lanza L, Bosco O, Imro MA, Scudeletti M, Indiveri F, Ferrone S: Increased level of serum HLA class I antigens in HIV infection. Correlation with disease progression. Hum Immunol 1994, 40:259-266.
- [16]Schwartz O, Marechal V, Le Gall S, Lemonnier F, Heard JM: Endocytosis of major histocompatibility complex class I molecules is induced by the HIV-1 Nef protein. Nat Med 1996, 2:338-342.
- [17]Lichterfeld M, Kavanagh DG, Williams KL, Moza B, Mui SK, Miura T, Sivamurthy R, Allgaier R, Pereyra F, Trocha A, et al.: A viral CTL escape mutation leading to immunoglobulin-like transcript 4-mediated functional inhibition of myelomonocytic cells. J Exp Med 2007, 204:2813-2824.
- [18]Jones DC, Kosmoliaptsis V, Apps R, Lapaque N, Smith I, Kono A, Chang C, Boyle LH, Taylor CJ, Trowsdale J, Allen RL: HLA Class I Allelic Sequence and Conformation Regulate Leukocyte Ig-Like Receptor Binding. J Immunol 2011.
- [19]Donaghy H, Gazzard B, Gotch F, Patterson S: Dysfunction and infection of freshly isolated blood myeloid and plasmacytoid dendritic cells in patients infected with HIV-1. Blood 2003, 101:4505-4511.
- [20]Stacey AR, Norris PJ, Qin L, Haygreen EA, Taylor E, Heitman J, Lebedeva M, DeCamp A, Li D, Grove D, et al.: Induction of a striking systemic cytokine cascade prior to peak viremia in acute human immunodeficiency virus type 1 infection, in contrast to more modest and delayed responses in acute hepatitis B and C virus infections. J Virol 2009, 83:3719-3733.
- [21]Valdez H, Lederman MM: Cytokines and cytokine therapies in HIV infection. AIDS Clin Rev 1997, 187-228.
- [22]Huang J, Burke P, Yang Y, Seiss K, Beamon J, Cung T, Toth I, Pereyra F, Lichterfeld M, Yu XG: Soluble HLA-G inhibits myeloid dendritic cell function in HIV-1 infection by interacting with leukocyte immunoglobulin-like receptor B2. J Virol 2010, 84:10784-10791.
- [23]Chang CC, Ciubotariu R, Manavalan JS, Yuan J, Colovai AI, Piazza F, Lederman S, Colonna M, Cortesini R, Dalla-Favera R, Suciu-Foca N: Tolerization of dendritic cells by T(S) cells: the crucial role of inhibitory receptors ILT3 and ILT4. Nat Immunol 2002, 3:237-243.
- [24]Hunt JS, Petroff MG, McIntire RH, Ober C: HLA-G and immune tolerance in pregnancy. FASEB J 2005, 19:681-693.
- [25]Carrington M, O'Brien SJ: The influence of HLA genotype on AIDS. Annu Rev Med 2003, 54:535-551.
- [26]Pereyra F, Jia X, McLaren PJ, Telenti A, de Bakker PI, Walker BD, Ripke S, Brumme CJ, Pulit SL, Carrington M, et al.: The major genetic determinants of HIV-1 control affect HLA class I peptide presentation. Science 2010, 330:1551-1557.
- [27]Huang J, Goedert JJ, Sundberg EJ, Cung TD, Burke PS, Martin MP, Preiss L, Lifson J, Lichterfeld M, Carrington M, Yu XG: HLA-B*35-Px-mediated acceleration of HIV-1 infection by increased inhibitory immunoregulatory impulses. J Exp Med 2009, 206:2959-66.
- [28]Tanabe M, Sekimata M, Ferrone S, Takiguchi M: Structural and functional analysis of monomorphic determinants recognized by monoclonal antibodies reacting with the HLA class I alpha 3 domain. J Immunol 1992, 148:3202-3209.