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Immunological fingerprints of controllers developing neutralizing HIV-1 antibodies

ABSTRACT: Immunological fingerprints of controllers developing neutralizing HIV-1 antibodies

PROVIDER: PRJNA593611 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR10588700_1.fastq.gz	Fastqsanger.gz
	SRR10588700_2.fastq.gz	Fastqsanger.gz
	SRR10588800_1.fastq.gz	Fastqsanger.gz
	SRR10588800_2.fastq.gz	Fastqsanger.gz
	SRR10588701_1.fastq.gz	Fastqsanger.gz

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Immunological fingerprints of controllers developing neutralizing HIV-1 antibodies

Project description:Induction of broadly neutralizing antibodies (bnAbs) is highly desired for an effective vaccine against HIV-1. Typically, bnAbs develop in patients with high viremia, but can also evolve in some untreated HIV-1 controllers with low viral loads. Here, we identify a subgroup of neutralizer-controllers characterized by myeloid DC (mDCs) with a distinct inflammatory signature and a superior ability to prime T follicular helper (Tfh)-like cells in an STAT4-dependent fashion. This distinct immune profile is associated with a higher frequency of Tfh-like cells in peripheral blood (pTfh) and an enrichment for Tfh-defining genes in circulating CD4+ T cells. Correspondingly, Monocytes from this neutralizer controller subgroup upregulate genes encoding for chemotaxis and inflammation, and secrete high levels of IL-12 in response to TLR stimulation. Together, our results suggest multi-compartment immune networks between mDCs, Tfh and Monocytes that might facilitate development of bnAbs in a subgroup of HIV-1 controllers.

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Immunological Fingerprints of Controllers Developing Neutralizing HIV-1 Antibodies.

Project description:The induction of broadly neutralizing antibodies (bnAbs) is highly desired for an effective vaccine against HIV-1. Typically, bnAbs develop in patients with high viremia, but they can also evolve in some untreated HIV-1 controllers with low viral loads. Here, we identify a subgroup of neutralizer-controllers characterized by myeloid DCs (mDCs) with a distinct inflammatory signature and a superior ability to prime T follicular helper (Tfh)-like cells in an STAT4-dependent fashion. This distinct immune profile is associated with a higher frequency of Tfh-like cells in peripheral blood (pTfh) and an enrichment for Tfh-defining genes in circulating CD4+ T cells. Correspondingly, monocytes from this neutralizer controller subgroup upregulate genes encoding for chemotaxis and inflammation, and they secrete high levels of IL-12 in response to TLR stimulation. Our results suggest the existence of multi-compartment immune networks between mDCs, Tfh, and monocytes that may facilitate the development of bnAbs in a subgroup of HIV-1 controllers.

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