Tags

Type your tag names separated by a space and hit enter

HIV-1 subtype C transmitted founders modulate dendritic cell inflammatory responses.
Retrovirology. 2020 Jul 02; 17(1):17.R

Abstract

BACKGROUND

Heterosexual transmission remains the main route of HIV-1 transmission and female genital tract (FGT) inflammation increases the risk of infection. However, the mechanism(s) by which inflammation facilitates infection is not fully understood. In rhesus macaques challenged with simian immunodeficiency virus, dendritic cell (DC) mediated recruitment of CD4+ T cells to the FGT was critical for infection. The aim of this study was to delineate the mechanisms underlying DC-mediated HIV infection by comparing chemokine and pro-inflammatory cytokine production in response to transmitted founder (TF) and chronic infection (CI) Envelope (Env) pseudotyped viruses (PSV).

RESULTS

Monocyte-derived DCs (MDDCs) were stimulated with PSV and recombinant gp140 representing matched TF and CI pairs of four individuals and cytokine secretion measured by multiplex immuno-assay. We found that 4/9 Env induced robust MDDC inflammatory responses and of those, three were cloned from TFs. Overall, TF Env induced MDDCs from healthy donors to secrete higher concentrations of inflammatory cytokines and chemokines than those from CI, suggesting TF Env were better inducers of inflammation. Assessing the signalling pathway associated with inflammatory cytokines, we found that PSV of matched TF and CI variants and a gp140 clone activated ERK and JNK to similar levels. Recombinant soluble DC-SIGN inhibited cytokine release and activation of ERK by PSV, suggesting that Env-DC-SIGN binding was partly involved in MDDC stimulation. Therefore, Env clones might differentially stimulate MDDC immune responses via alternative, yet unidentified signalling pathways.

CONCLUSION

Overall, this could suggest that the genetics of the virus itself influences inflammatory responses during HIV infection. In the absence of pre-existing infections, induction of greater inflammatory response by TFs might favour virus survival within the healthy FGT by driving an influx of target cells to sites of infection while suppressing immune responses via IL-10.

Authors+Show Affiliations

Division of Cardiology, Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa. lumngwena@yahoo.co.uk. Institute of Infectious Diseases and Molecular Medicine (IDM), University of Cape Town, Cape Town, South Africa. lumngwena@yahoo.co.uk. Centre for the Study of Emerging and Re-emerging Infections (CREMER) and Virology Laboratory, Institute for Medical Research and Medicinal Plant Studies (IMPM), Ministry of Scientific Research and Innovation (MINRESI), Yaounde, Cameroon. lumngwena@yahoo.co.uk.National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, MD, USA.Disease Elimination Program, Life Sciences Discipline, Burnet Institute, Melbourne, Australia.National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, MD, USA.National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, MD, USA.Department of Integrative Biomedical Sciences (IBMS), Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa. Zl.woodman@uct.ac.za.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32615983

Citation

Lumngwena, Evelyn Ngwa, et al. "HIV-1 Subtype C Transmitted Founders Modulate Dendritic Cell Inflammatory Responses." Retrovirology, vol. 17, no. 1, 2020, p. 17.
Lumngwena EN, Metenou S, Masson L, et al. HIV-1 subtype C transmitted founders modulate dendritic cell inflammatory responses. Retrovirology. 2020;17(1):17.
Lumngwena, E. N., Metenou, S., Masson, L., Cicala, C., Arthos, J., & Woodman, Z. (2020). HIV-1 subtype C transmitted founders modulate dendritic cell inflammatory responses. Retrovirology, 17(1), 17. https://doi.org/10.1186/s12977-020-00526-0
Lumngwena EN, et al. HIV-1 Subtype C Transmitted Founders Modulate Dendritic Cell Inflammatory Responses. Retrovirology. 2020 Jul 2;17(1):17. PubMed PMID: 32615983.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - HIV-1 subtype C transmitted founders modulate dendritic cell inflammatory responses. AU - Lumngwena,Evelyn Ngwa, AU - Metenou,Simon, AU - Masson,Lindi, AU - Cicala,Claudia, AU - Arthos,James, AU - Woodman,Zenda, Y1 - 2020/07/02/ PY - 2020/02/24/received PY - 2020/06/24/accepted PY - 2020/7/4/entrez PY - 2020/7/4/pubmed PY - 2020/7/4/medline KW - HIV-subtype C Env KW - Immunosuppression KW - Inflammatory responses KW - Transmission KW - Transmitter/Founder Envelopes KW - Virus survival SP - 17 EP - 17 JF - Retrovirology JO - Retrovirology VL - 17 IS - 1 N2 - BACKGROUND: Heterosexual transmission remains the main route of HIV-1 transmission and female genital tract (FGT) inflammation increases the risk of infection. However, the mechanism(s) by which inflammation facilitates infection is not fully understood. In rhesus macaques challenged with simian immunodeficiency virus, dendritic cell (DC) mediated recruitment of CD4+ T cells to the FGT was critical for infection. The aim of this study was to delineate the mechanisms underlying DC-mediated HIV infection by comparing chemokine and pro-inflammatory cytokine production in response to transmitted founder (TF) and chronic infection (CI) Envelope (Env) pseudotyped viruses (PSV). RESULTS: Monocyte-derived DCs (MDDCs) were stimulated with PSV and recombinant gp140 representing matched TF and CI pairs of four individuals and cytokine secretion measured by multiplex immuno-assay. We found that 4/9 Env induced robust MDDC inflammatory responses and of those, three were cloned from TFs. Overall, TF Env induced MDDCs from healthy donors to secrete higher concentrations of inflammatory cytokines and chemokines than those from CI, suggesting TF Env were better inducers of inflammation. Assessing the signalling pathway associated with inflammatory cytokines, we found that PSV of matched TF and CI variants and a gp140 clone activated ERK and JNK to similar levels. Recombinant soluble DC-SIGN inhibited cytokine release and activation of ERK by PSV, suggesting that Env-DC-SIGN binding was partly involved in MDDC stimulation. Therefore, Env clones might differentially stimulate MDDC immune responses via alternative, yet unidentified signalling pathways. CONCLUSION: Overall, this could suggest that the genetics of the virus itself influences inflammatory responses during HIV infection. In the absence of pre-existing infections, induction of greater inflammatory response by TFs might favour virus survival within the healthy FGT by driving an influx of target cells to sites of infection while suppressing immune responses via IL-10. SN - 1742-4690 UR - https://www.unboundmedicine.com/medline/citation/32615983/HIV-1_subtype_C_transmitted_founders_modulate_dendritic_cell_inflammatory_responses L2 - https://retrovirology.biomedcentral.com/articles/10.1186/s12977-020-00526-0 DB - PRIME DP - Unbound Medicine ER -
Try the Free App:
Prime PubMed app for iOS iPhone iPad
Prime PubMed app for Android
Prime PubMed is provided
free to individuals by:
Unbound Medicine.