ntiviral Response Induced by Toll-Like Receptor (TLR) 7/TLR8 Activation Inhibits Human Immunodeficiency Virus Type 1 Infection in Cord Blood Macrophage

Author(s)

Pietrobon, Anna J. ^{[1, 2]} ; Yoshikawa, Fabio S. Y. ^{[2, 3]} ; Oliveira, Luana M. ^[2] ; Pereira, Natalli Z. ^[2] ; Matozo, Tais ^[1] ; de Alencar, Bruna C. ^[1] ; Duarte, Alberto J. S. ^[2] ; Sato, Maria N. ^[2]

Affiliation

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Med Sch, Trop Med Inst Sao Paulo, LIM 56, Dept Dermatol, Lab Dermatol & Immunodeficiencies, Av Dr Eneas de Carvalho Aguiar 470, 3rd Floor, BR-05403000 Sao Paulo - Brazil

^[3] Chiba Univ, Med Mycol Res Ctr, Div Mol Immunol, Chiba - Japan

• Document type: Journal article
• Source: Journal of Infectious Diseases; v. 225, n. 3, p. 510-519, FEB 1 2022.
• Web of Science Citations: 0

Abstract

Cord blood macrophages are more susceptible to HIV-1 infection. This vulnerability can be reversed under treatment with the type I interferon adjuvant CL097, which triggers inflammatory and antiviral responses in these cells, attenuating viral replication. Vertical transmission is the main mechanism of human immunodeficiency virus type 1 (HIV-1) infection in infants, who may develop high viremia and rapidly progress to AIDS. Innate immunity agonists can control HIV-1 replication in vitro, but the protective effect in the neonatal period remains unknown. Herein, we evaluated the immunomodulatory and antiviral effects of type I interferon (IFN-I) adjuvants on cord blood monocyte-derived macrophages upon HIV-1 infection. Despite the phenotypic and transcriptional similarities between cord blood and adult macrophages, cord blood cells were prone to viral replication when infected with HIV-1. However, treatment with CL097 efficiently promoted the antiviral and inflammatory responses and inhibited HIV-1 replication in cord blood cells in an NF-kappa B and autophagy activation-independent manner. Our data suggest that cord blood macrophages are able to establish antiviral responses induced by IFN-I adjuvants similar to those of their adult counterparts, revealing a potential adjuvant candidate to enhance the neonatal immune response. (AU)

• FAPESP's process: 16/01269-1 - Immunomodulation of cytosolic DNA sensors by type I interferon adjuvants in macrophages of newborn in vitro infected with HSV-1 and HIV-1
• Grantee: Anna Julia Pietrobon
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 16/16840-6 - Analysis of antiviral factors and exosomes in trophoblasts and newborn monocytes in Zika virus in vitro infection
• Grantee: Maria Notomi Sato
• Support Opportunities: Regular Research Grants