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Neutrophil Subtypes Shape HIV-specific CD8 T Cell Responses After Vaccinia Virus Infection.

ABSTRACT: Neutrophil Subtypes Shape HIV-specific CD8 T Cell Responses After Vaccinia Virus Infection.

PROVIDER: PRJNA693704 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13496141.fastq.gz	Fastqsanger.gz
	SRR13496142.fastq.gz	Fastqsanger.gz
	SRR13496143.fastq.gz	Fastqsanger.gz
	SRR13496144.fastq.gz	Fastqsanger.gz
	SRR13496145.fastq.gz	Fastqsanger.gz

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Neutrophil Subtypes Shape HIV-specific CD8 T Cell Responses After Vaccinia Virus Infection.

Project description:Neutrophils are innate immune cells involved in the elimination of pathogens. Recent studies showed that neutrophils can also act as antigen presenting cells (APC) to induce adaptive immune responses. Specific neutrophil populations (Na and Nb) with different levels of APC markers and in vitro distinct capacity to generate vaccinia virus (VACV)-specific CD8 T cell responses have been shown. However, how these neutrophil subtypes exert their role in vivo and how manipulation of Nb/Na ratio can influence vaccine-mediated immune responses are not known. In the context of VACV infection, we characterized HIV-specific CD8 T cell responses, delineated neutrophil transcriptomic profiles and described neutrophil dynamic behaviors in the spleen. By splenic multiphoton intravital microscopy (MV-IVM), we could distinguish both neutrophil subtypes and found that they showed distinct migratory and motility patterns and different ability to interact with CD8 T cells and move towards them. After analysis of adhesion, inflammatory and migration receptors from peritoneal cavity, blood and spleen, we defined that Nb neutrophils overexpressed the trans-endothelial migration marker a4b1integrin compared to Na subtype. Finally, by inhibiting a4b1integrin, we increased the Nb/Na ratio in peritoneal cavity and spleen, and in turn enhanced CD8 T cell responses to HIV-antigens. These findings provide significant advancements in the comprehension of neutrophil-based control of adaptive immune system. These results are relevant in vaccine vector design that could induce distinct neutrophil subtypes and, in consequence modulate antigen-specific T cell responses.

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Transcriptional expression data from vaccinia/HIV-1 vaccine immunized healthy subjects [in vivo]

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2020-12-31 | GSE118976 | GEO

Neutrophil subtypes shape HIV-specific CD8 T-cell responses after vaccinia virus infection.

Project description:Neutrophils are innate immune cells involved in the elimination of pathogens and can also induce adaptive immune responses. Nα and Nβ neutrophils have been described with distinct in vitro capacity to generate antigen-specific CD8 T-cell responses. However, how these cell types exert their role in vivo and how manipulation of Nβ/Nα ratio influences vaccine-mediated immune responses are not known. In this study, we find that these neutrophil subtypes show distinct migratory and motility patterns and different ability to interact with CD8 T cells in the spleen following vaccinia virus (VACV) infection. Moreover, after analysis of adhesion, inflammatory, and migration markers, we observe that Nβ neutrophils overexpress the α4β1 integrin compared to Nα. Finally, by inhibiting α4β1 integrin, we increase the Nβ/Nα ratio and enhance CD8 T-cell responses to HIV VACV-delivered antigens. These findings provide significant advancements in the comprehension of neutrophil-based control of adaptive immune system and their relevance in vaccine design.

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Modified Vaccinia virus Ankara vector induces specific cellular and humoral responses in the female reproductive tract, the main HIV portal of entry

Project description:The female reproductive tract is one of the major mucosal invasion site of HIV-1. This site has been neglected in previous HIV-1 vaccine studies. Immune responses in the female reproductive tract after systemic vaccination remain to be characterized. Using a modified vaccinia virus Ankara (MVA) as a vaccine model, we characterized specific immune responses in all compartments of the female reproductive tract (FRT) of non-human primates after systemic vaccination. Memory T cells were preferentially found in the lower tract (vagina and cervix), whereas antigen-presenting cells and innate lymphoid cells were mainly located in the upper tract (uterus and fallopian tubes). This compartmentalisation of immune cells in the FRT was supported by transcriptomic analyses and correlation network. Polyfunctional MVA-specific CD8+ T cells were detected in the blood, lymph nodes, vagina, cervix, uterus and fallopian tubes. Anti-MVA IgG and IgA were detected in cervicovaginal fluid after a second vaccine dose. Systemic vaccination with an MVA vector thus elicits cellular and antibody responses in the female reproductive tract.

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Transcriptional expression data from vaccinia/HIV-1 vaccine immunized healthy subjects [in vivo]

Project description:Transcriptional expression data from vaccinia/HIV-1 vaccine immunized healthy subjects [in vivo]

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