Toll-like Receptor Agonists Enhance HIV-specific T Cell Response Mediated by Plasmacytoid Dendritic Cells in Diverse HIV-1 Disease Progression Phenotypes

doi:10.21203/rs.3.rs-1741647/v1

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Toll-like Receptor Agonists Enhance HIV-specific T Cell Response Mediated by Plasmacytoid Dendritic Cells in Diverse HIV-1 Disease Progression Phenotypes

https://doi.org/10.21203/rs.3.rs-1741647/v1

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Plasmacytoid dendritic cells (pDCs) sense viral and bacterial products through Toll-like receptor (TLR)-7 and -9 and translate this sensing in Interferon-α (IFN-α) production and T cell polarization. These cells are considered a link between innate and adaptive immunity, inducing and maintaining antigen-specific T cell responses and contributing to the control and eventually to the chronic immune activation and disease progression in HIV-1 infection scenario. The understanding of the mechanisms involved in pDCs stimulation may contribute to immunotherapeutic strategies aiming to decrease HIV-1 reservoir. The objective of the present study was to characterize the immunomodulatory effects of TLR agonist stimulations through a pDC/T cell coculture in different HIV-1 disease progression phenotypes and healthy donors (HD). pDCs were previously stimulated with AT-2-HIV-1, CpGA, CpGC and GS9620. After coculture with autologous CD4 or CD8 T cells we observed an increase of pDCs activation markers levels, interferon related genes, HIV-1 restriction factors and cytokines levels. This pDCs coordinate activation was prominent with CpG-C and GS9620 and induced an increase of HIV-specific T cell response. This pDCs dependent HIV-1 specific T-cell response was associated with the upregulation of HIV-1 restriction factors and IFN-α production. Interestingly, pDCs activation in people on ART was similar to that found in people that spontaneously control the virus. These results shed light on the mechanisms associated with TLR-specific pDCs stimulation associated with T cell polarization for eliciting antiviral response which is essential for HIV eradication strategies.

Table 1_ Characteristics of the studied participants.

	HD (n=21)	HIV VIR (n=7)	HIV IR (n=6)	HIV INR (n=6)	HIV EC (n=4)
Male sex, n (%)	15 (71.42)	7(100)	5(83.3)	6(100)	3(75)
Age, (years)	42 [35-51]	36 [32 - 45]	50 [41 - 62]	56 [49 - 60]	48 [37 - 57]
CD4 Nadir counts, (cells/µl)	NA	376 [273 - 448]	162 [75 - 310]	42 [36 - 86]	615 [459 - 697]
CD4⁺T-cell counts, (cells/µl)	NA	354 [299 - 456]	724 [536 - 1022]	277 [157 - 322]	738 [611 - 940]
CD8⁺T-cell counts, (cells/µl)	NA	773 [527 - 1148]	592 [376 - 1011]	711 [423 - 1561]	543 [477 - 585]
CD4+/ CD8+ T Cell ratio	NA	0.5 [0.33 - 0.71]	1.38 [0.91 - 1.41]	0.36 [0.18 - 0.51]	1.3 [1.22 - 1.73]
Anti-HCV n (%)	0(0)	0 (0)	0 (0)	3 (50)	2 (50)
HIV RNA (Log₁₀ copies/ml)	0(0)	4.80 [3.73 - 4.96]	1.60 [1.60 - 1.60]	1.60 [1.60 - 1.60]	1.61 [1.60 - 1.93]

Values are given as No. (%) for categorical variables or median (interquartile ranges [IQR]) for continuous variables. Abbreviation: NA, not applicable; HCV, hepatitis C virus; HIV, human immunodeficiency virus; IQR, interquartile range; HD, Healthy Donors; VIR, Viremic; IR, Immune Responders; INR, Immune Non Responders and EC, HIV Elite Controllers and.

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Toll-like Receptor Agonists Enhance HIV-specific T Cell Response Mediated by Plasmacytoid Dendritic Cells in Diverse HIV-1 Disease Progression Phenotypes

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