scholarly journals Single-cell RNA-Seq analysis reveals dual sensing of HIV-1 in blood Axl+ dendritic cells

2022 ◽  
Author(s):  
Flavien Brouiller ◽  
Francesca Nadalin ◽  
Ouardia Aït-Mohamed ◽  
Pierre-Emmanuel Bonté ◽  
Constance Delaugerre ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cd4 T Cell ◽  
Type I ◽  
Rna Seq ◽  
Innate Response ◽  
Viral Response ◽  
Hiv 1 ◽  
Dc Maturation

Sensing of incoming viruses represents one of the pivotal tasks of dendritic cells (DC). Human primary blood DC encompass various subsets that are diverse in their susceptibility and response to HIV-1. The recent identification of Axl+DC, a new blood DC subset, endowed with unique capacities to bind, replicate, and transmit HIV-1 prompted us to evaluate its anti-viral response. We show that HIV-1 induced two main broad and intense transcriptional programs in different Axl+DC potentially induced by different sensors; a NF-κB-mediated program that led to DC maturation and efficient antigen-specific CD4+T cell activation, and a program mediated by STAT1/2 that activated type I IFN and an ISG response. These responses were absent from cDC2 exposed to HIV-1 except when viral replication occurred. Finally, Axl+DC actively replicating HIV-1 identified by quantification of viral transcripts exhibited a mixed NF-κB/ISG innate response. Our results suggest that the route of HIV-1 entry may dictate different innate sensing pathway by DC.

The potential impact of CD4+ T cell activation and enhanced Th1/Th2 cytokine ratio on HIV-1 secretion in the lungs of individuals with advanced AIDS and active pulmonary infection

2011 ◽  
Vol 139 (2) ◽  
pp. 142-154 ◽  
Author(s):  
Pierre-Alain Rubbo ◽  
Edouard Tuaillon ◽  
Karine Bolloré ◽  
Vincent Foulongne ◽  
Arnaud Bourdin ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Pulmonary Infection ◽  
Cd4 T Cell ◽  
Th2 Cytokine ◽  
Potential Impact ◽  
Hiv 1

scholarly journals HIV-specific T-cell Responses and Generalized Activation in HIV-1 Infected Long-term Non-progressors and Progressors from South India

2019 ◽  
Vol 16 (4) ◽  
pp. 302-314
Author(s):  
Chinnambedu Ravichandran Swathirajan ◽  
Ramachandran Vignesh ◽  
Greer Waldrop ◽  
Uma Shanmugasundaram ◽  
Pannerselvam Nandagopal ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cd4 T Cell ◽  
Cell Responses ◽  
Activation Rates ◽  
Hiv 1

Background:Anti-viral cytokine expressions by cytotoxic T-cells and lower activation rates have been reported to correlate with suppressed HIV replication in long-term non-progressors (LTNP). Immune mechanisms underlying disease non-progression in LTNP might vary with HIV-1 subtype and geographical locations.Objective:This study evaluates cytokine expression and T-cells activation in relation to disease non-progression in LTNP.Methods:HIV-1 Subtype C infected LTNP (n=20) and progressors (n=15) were enrolled and flowcytometry assays were performed to study HIV-specific CD8 T-cells expressing IL-2, IFN-γ, TNF-α and MIP-1β against gag and env peptides. CD4+ T-cell activation was evaluated by surface expression of HLADR and CD38.Results:Proportions of cytokines studied did not differ significantly between LTNP and progressors, while contrasting correlations with disease progression markers were observed in LTNP. CD4+ T-cell activation rates were significantly lower in LTNP compared to progressors which indicate the potential role of T-cell activation rates in disease non-progression in LTNP.Conclusion:LTNP and progressors showed similar CD8+ T-cell responses, but final conclusions can be drawn only by comparing multiple immune factors in larger LTNP cohort with HIV-1 infected individuals at various levels of disease progression. A possible role of HIV-1 subtype variation and ethnic differences in addition to host-genetic and viral factors cannot be ruled out.

scholarly journals Contact-dependent delivery of IL-2 by dendritic cells to CD4 T cells in the contraction phase promotes their long-term survival

2019 ◽  
Vol 11 (2) ◽  
pp. 108-123
Author(s):  
Dan Tong ◽  
Li Zhang ◽  
Fei Ning ◽  
Ying Xu ◽  
Xiaoyu Hu ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cd4 T Cells ◽  
Cell Activation ◽  
Cd4 T Cell ◽  
Immune Memory ◽  
Term Survival

Abstract Common γ chain cytokines are important for immune memory formation. Among them, the role of IL-2 remains to be fully explored. It has been suggested that this cytokine is critically needed in the late phase of primary CD4 T cell activation. Lack of IL-2 at this stage sets for a diminished recall response in subsequent challenges. However, as IL-2 peak production is over at this point, the source and the exact mechanism that promotes its production remain elusive. We report here that resting, previously antigen-stimulated CD4 T cells maintain a minimalist response to dendritic cells after their peak activation in vitro. This subtle activation event may be induced by DCs without overt presence of antigen and appears to be stronger if IL-2 comes from the same dendritic cells. This encounter reactivates a miniature IL-2 production and leads a gene expression profile change in these previously activated CD4 T cells. The CD4 T cells so experienced show enhanced reactivation intensity upon secondary challenges later on. Although mostly relying on in vitro evidence, our work may implicate a subtle programing for CD4 T cell survival after primary activation in vivo.

Increased levels of CD4 T-cell activation in individuals with CXCR4 using viruses in primary HIV-1 infection

AIDS ◽  
2012 ◽  
Vol 26 (7) ◽  
pp. 887-890 ◽  
Author(s):  
Elizabeth Hamlyn ◽  
Stephen Hickling ◽  
Kholoud Porter ◽  
John Frater ◽  
Rodney Phillips ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cd4 T Cell ◽  
Hiv 1

Thyroglobulin-pulsed human monocyte-derived dendritic cells induce CD4+ T cell activation

2004 ◽  
Author(s):  
Mariko Morishita ◽  
Kaoru Uchimaru ◽  
Katsuaki Sato ◽  
Akira Ohtsuru ◽  
Shunichi Yamashita ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Human Monocyte ◽  
Cd4 T Cell

scholarly journals Identification of crassin acetate as a new immunosuppressant triggering heme oxygenase-1 expression in dendritic cells

Blood ◽  
2009 ◽  
Vol 114 (1) ◽  
pp. 64-73 ◽  
Author(s):  
Hironori Matsushima ◽  
Hiroaki Tanaka ◽  
Norikatsu Mizumoto ◽  
Akira Takashima
Keyword(s):  
Dendritic Cells ◽  
Heme Oxygenase ◽  
T Cell Activation ◽  
Large Scale ◽  
Cell Activation ◽  
Contact Hypersensitivity ◽  
Heme Oxygenase 1 ◽  
Mixed Leukocyte Reaction ◽  
Cellular Targets ◽  
Dc Maturation

Abstract By screening 720 natural compounds in a standard 2-way allogeneic mixed leukocyte reaction assay, we identified a potent immunosuppressive capacity of crassin acetate (CRA), a coral-derived cembrane diterpenoid. CRA efficiently inhibited allogeneic mixed leukocyte reaction as well as antigen-specific activation of CD4 T cells by bone marrow–derived dendritic cells (DCs). With regard to cellular targets, CRA suppressed not only mitogen-triggered T-cell activation, but also lipopolysaccharide-induced DC maturation, indicating dual functionality. Treatment with CRA at nontoxic doses induced heme oxygenase-1 (HO-1) mRNA/protein expression and HO-1 enzymatic activity in DCs, suggesting a unique mechanism of action. In fact, lipopolysaccharide-induced DC maturation was also inhibited by structurally unrelated compounds known to induce HO-1 expression or carbon monoxide (CO) release. Allergic contact hypersensitivity response to oxazolone and oxazolone-induced Langerhans cell migration from epidermis were both prevented almost completely by systemic administration of CRA. Not only do our results support the recent concept that HO-1/CO system negatively regulates immune responses, they also form both conceptual and technical frameworks for a more systematic, large-scale drug discovery effort to identify HO-1/CO-targeted immunosuppressants with dual target specificity.

scholarly journals Dendritic Cell Responses to Early Murine Cytomegalovirus Infection

2003 ◽  
Vol 197 (7) ◽  
pp. 885-898 ◽  
Author(s):  
Marc Dalod ◽  
Tanya Hamilton ◽  
Rachelle Salomon ◽  
Thais P. Salazar-Mather ◽  
Stanley C. Henry ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
T Cell Activation ◽  
Cell Activation ◽  
Lymphocyte Activation ◽  
Murine Cytomegalovirus ◽  
Cell Responses ◽  
Dc Maturation

Differentiation of dendritic cells (DCs) into particular subsets may act to shape innate and adaptive immune responses, but little is known about how this occurs during infections. Plasmacytoid dendritic cells (PDCs) are major producers of interferon (IFN)-α/β in response to many viruses. Here, the functions of these and other splenic DC subsets are further analyzed after in vivo infection with murine cytomegalovirus (MCMV). Viral challenge induced PDC maturation, their production of high levels of innate cytokines, and their ability to activate natural killer (NK) cells. The conditions also licensed PDCs to efficiently activate CD8 T cells in vitro. Non-plasmacytoid DCs induced T lymphocyte activation in vitro. As MCMV preferentially infected CD8α+ DCs, however, restricted access to antigens may limit plasmacytoid and CD11b+ DC contribution to CD8 T cell activation. IFN-α/β regulated multiple DC responses, limiting viral replication in all DC and IL-12 production especially in the CD11b+ subset but promoting PDC accumulation and CD8α+ DC maturation. Thus, during defense against a viral infection, PDCs appear specialized for initiation of innate, and as a result of their production of IFN-α/β, regulate other DCs for induction of adaptive immunity. Therefore, they may orchestrate the DC subsets to shape endogenous immune responses to viruses.

scholarly journals Immunogenicity and safety of an inactivated SARS-CoV-2 vaccine in people living with HIV-1

2021 ◽  
Author(s):  
Yanmeng Feng ◽  
Yifan Zhang ◽  
Zhangyufan He ◽  
Haojie Huang ◽  
Xiangxiang Tian ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cd8 T Cell ◽  
Cd4 T Cell ◽  
People Living With Hiv ◽  
Healthy Individuals ◽  
Cell Counts ◽  
Living With Hiv ◽  
Hiv 1

Background It has been proven that inactivated COVID-19 vaccines are safe and effective in general population with intact immunity. However, their safety and immunogenicity have not been demonstrated in people living with HIV (PLWH). Methods 42 HIV-1 infected individuals who were stable on cART and 28 healthy individuals were enrolled in this study. Two doses of an inactivated COVID-19 vaccine (BIBP-CorV) were given 4 weeks apart. The safety and reactogenicity of the vaccine were evaluated by observing clinical adverse events and solicited local and systemic reactions. Humoral responses were measured by anti-spike IgG ELISA and surrogate neutralization assays. Cell-mediated immune responses and vaccine induced T cell activation were measured by flow cytometry. Findings All the HIV-1 infected participants had a CD4+ T cell count of above 200 cells/μL both at baseline and 4 weeks after vaccination. No solicited adverse reaction was observed among all participants. Similar binding antibody, neutralizing antibody and S protein specific T cell responses were elicited in PLWH and healthy individuals. Further analyses showed that PLWH with low baseline CD4+/CD8+ T cell ratios (<0.6) generated lower antibody responses after vaccination than PLWH with medium (0.6~1.0) or high (≥1.0) baseline CD4+/CD8+ T cell ratios (P<0.01). The CD3+, CD4+ and CD8+ T cell counts of PLWH decreased significantly after vaccination, but it did not lead to any adverse clinical manifestation. Moreover, we found that the general burden of HIV-1 among the PLWH cohort decreased significantly (P=0.0192) after vaccination. And the alteration of HIV-1 viral load was not significantly associated with the vaccine induced CD4+ T cell activation. Interpretation Our data demonstrate that the inactivated COVID-19 vaccine is safe and immunogenic in PLWH who are stable on cART with unsuppressed CD4 counts. Funding This work was funded by the National Natural Science Foundation of China (Grant No. 81971559, 82041010).

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