HIV Impairment of Immune Responses in Dendritic Cells

Abstract

Dendritic cells and their subsets are diverse populations of immune cells in the skin and mucous membranes that possess the ability to sense the presence of microbes and orchestrate an efficient and adapted immune response. Dendritic cells (DC) have the unique ability to act as a bridge between the innate and adaptive immune responses. These cells are composed of a number of subsets behaving with preferential and specific features depending on their location and surrounding environment. Langerhans cells (LC) or dermal DC (dDC) are readily present in mucosal areas. Other DC subsets such as plasmacytoid DC (pDC), myeloid DC (myDC), or monocyte-derived DC (MDDC) are thought to be recruited or differentiated in sites of pathogenic challenge. Upon HIV infection, DC and their subsets are likely among the very first immune cells to encounter incoming pathogens and initiate innate and adaptive immune responses. However, as evidenced during HIV infection, some pathogens have evolved subtle strategies to hijack key cellular machineries essential to generate efficient antiviral responses and subvert immune responses for spread and survival.In this chapter, we review recent research aimed at investigating the involvement of DC subtypes in HIV transmission at mucosal sites, concentrating on HIV impact on cellular signalling and trafficking pathways in DC leading to DC-mediated immune response alterations and viral immune evasion. We also address some aspects of DC functions during the chronic immune pathogenesis and conclude with an overview of the current and novel therapeutic and prophylactic strategies aimed at improving DC-mediated immune responses, thus to potentially tackle the early events of mucosal HIV infection and spread.

Serum selenium and skin diseases among Nigerians with human immunodeficiency virus/acquired immune deficiency syndrome

“…Low levels of serum selenium will therefore prevent proper functioning of the skin immune system giving way to opportunistic infections, such as oral candidiasis and skin malignancy. It is also known that HIV induces the loss of functional immunocompetent cells27 (including impairment of the skin immune system) leading to the manifestation of a plethora of skin diseases 29–31. The destruction of CD4+ vector and effector cells has been recognized as an important contributor to the pathogenesis of most of the cutaneous manifestations of HIV 29–31.…”

“…It is also known that HIV induces the loss of functional immunocompetent cells27 (including impairment of the skin immune system) leading to the manifestation of a plethora of skin diseases 29–31. The destruction of CD4+ vector and effector cells has been recognized as an important contributor to the pathogenesis of most of the cutaneous manifestations of HIV 29–31. Nail hyper pigmentation has significant association with low serum selenium in this study; the same has been associated with low CD4 count in a previous African study 24…”

HIV induced suppression of host immunity: relevance to <i>Mycobacterium tuberculosis</i> infections

“…Thus, these pre-activated cells encounter the virus and significantly delay their progress. For an example, TLR-4 ligand suppresses the HIV-1 replication in mφ [119,120]. To utilize the non-specific nature of innate immune activation, co-infection with commensal bacteria and parasite e.g., Trypanosoma cruzi inhibits the replication of HIV-1 within mφ.…”

“…To utilize the non-specific nature of innate immune activation, co-infection with commensal bacteria and parasite e.g., Trypanosoma cruzi inhibits the replication of HIV-1 within mφ. These organisms express many PAMPs, which triggers various TLRs on the surface/endocytic vesicles in MyD88 dependent manner [119][120][121][122]. However, HIV is known to inhibit TLR signalling by down-regulating IRAK-4 involved in downstream signalling [123].…”

Genetic characterisation of Langerin gene in human immunodeficiency virus-1-infected women from Bahia, Brazil

“…Dendritic cells (DCs) play an important role in early human immunodeficiency virus (HIV)-1 infection due to their ability to mostly capture the virus in peripheral tissues, such as the genital mucosa; migrate to the secondary lymphoid organs and present processed HIV-1 antigens to CD4 T lymphocytes, their major cell target (Ahmed et al 2013). Different DC subsets interact with HIV-1 via selected C-type lectin receptors (CLRs), independently of CD4 and chemokine co-receptors (CCR5 and CXCR4), which is the classical pathway used by HIV-1 to enter CD4 T lymphocytes and macrophages.…”