Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 Jan 30:14:1104423.
doi: 10.3389/fimmu.2023.1104423. eCollection 2023.

The initial interplay between HIV and mucosal innate immunity

Valeria Caputo  1 , Martina Libera  1 , Sofia Sisti  1 , Benedetta Giuliani  1 , Roberta A Diotti  1 , Elena Criscuolo  1
Affiliations
Review

The initial interplay between HIV and mucosal innate immunity

Valeria Caputo et al. Front Immunol. .

Abstract

Human Immunodeficiency Virus (HIV) is still one of the major global health issues, and despite significant efforts that have been put into studying the pathogenesis of HIV infection, several aspects need to be clarified, including how innate immunity acts in different anatomical compartments. Given the nature of HIV as a sexually transmitted disease, one of the aspects that demands particular attention is the mucosal innate immune response. Given this scenario, we focused our attention on the interplay between HIV and mucosal innate response: the different mucosae act as a physical barrier, whose integrity can be compromised by the infection, and the virus-cell interaction induces the innate immune response. In addition, we explored the role of the mucosal microbiota in facilitating or preventing HIV infection and highlighted how its changes could influence the development of several opportunistic infections. Although recent progress, a proper characterization of mucosal innate immune response and microbiota is still missing, and further studies are needed to understand how they can be helpful for the formulation of an effective vaccine.

Keywords: HIV; innate immunity; microbiome; mucosae; sexual transmitted disease.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
The immune components of mucosal barriers involved in HIV transmission. The extracellular environments of the oral, rectal, vaginal, and foreskin mucosae are diverse in their tissue architecture and characterized by numerous secreted factors that can hinder the mucosal transmission of HIV. In addition, saliva, foreskin secretion, and mucus are barrier-trapping and inactivating virions. Between the cells of the stratified epithelia and at their basal layers, the immune cells are present and recruited when HIV bypasses the first mechanism of defense.
Figure 2
Figure 2
Blocking mechanism of HIV infection in the mucosae. HIV requires the binding between the envelope protein gp120, the cellular receptor CD4, and other co-receptors, such as CXCR4, CCR5, and heparan sulfate proteoglycans (HPSG). However, the mucosal microenvironment may present some soluble factors that can block the infection by several mechanisms: 1) Mucins interact with the virions, causing their agglutination; 2) Agglutinins and mucins can strip gp120 from the viral envelope; 3) immunoglobulins, thrombospondin and proline-rich proteins bind gp120 preventing its interaction with CD4 on target cells; 4) Defensins and lactoferrin recognize HPSG and HIV co-receptors (CXCR4/CCR5) on the surface of susceptible cells and compete with gp120 for their binding; 5) Defensins and IFNs secreted by stimulated immune cells (e.g. Dendritic cells) led to CXCR4 downregulation and APOBEC3G induction, an antiviral restriction factor.
Figure 3
Figure 3
Microbiota characterization in HIV patients. The microbiota present in the mucosae can support or penalize HIV infection, and its changes can influence the development of several opportunistic infections. Numerous studies analyzing HIV-infected and -uninfected patients’ mucosal samples identified a different microbiota between the two populations: some species were higher in healthy controls (species reported in green) and others were more abundant during infection (species in red).
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Frescura L, Godfrey-Faussett P A, El-Sadr W, Syarif O, Ghys PD. Group on and behalf of the 2025 testing treatment target w. achieving the 95 95 95 targets for all: A pathway to ending AIDS. PloS One (2022) 17:e0272405. doi: 10.1371/journal.pone.0272405 - DOI - PMC - PubMed
    1. HIV.gov . HIV.gov global statistics (2022). Available at: https://www.hiv.gov/hiv-basics/overview/data-and-trends/global-statistics (Accessed November 15, 2022).
    1. Shi Y, Su J, Chen R, Wei W, Yuan Z, Chen X, et al. . The role of innate immunity in natural elite controllers of HIV-1 infection. Front Immunol (2022) 13:780922. doi: 10.3389/fimmu.2022.780922 - DOI - PMC - PubMed
    1. Saez R, Echaniz P, Juan MDD, Iribarren JA, Cuadrado E. The impaired response of NK cells from HIV-infected progressor patients to a-class CpG oligodeoxynucleotides is largely dependent of a decreased production of IL-12. Immunol Lett (2007) 109:83–90. doi: 10.1016/j.imlet.2007.01.006 - DOI - PubMed
    1. Herbeuval J-P, Nilsson J, Boasso A, Hardy AW, Kruhlak MJ, Anderson SA, et al. . Differential expression of IFN-α and TRAIL/DR5 in lymphoid tissue of progressor versus nonprogressor HIV-1-infected patients. Proc Natl Acad Sci (2006) 103:7000–5. doi: 10.1073/pnas.0600363103 - DOI - PMC - PubMed
-