CCR5 and CCR5Δ32 in bacterial and parasitic infections: Thinking chemokine receptors outside the HIV box

Abstract

The CCR5 molecule was reported in 1996 as the main HIV‐1 co‐receptor. In that same year, the CCR5Δ32 genetic variant was described as a strong protective factor against HIV‐1 infection. These findings led to extensive research regarding the CCR5, culminating in critical scientific advances, such as the development of CCR5 inhibitors for the treatment of HIV infection. Recently, the research landscape surrounding CCR5 has begun to change. Different research groups have realized that, since CCR5 has such important effects in the chemokine system, it could also affect other different physiological systems. Therefore, the effect of reduced CCR5 expression due to the presence of the CCR5Δ32 variant began to be further studied. Several studies have investigated the role of CCR5 and the impacts of CCR5Δ32 on autoimmune and inflammatory diseases, various types of cancer, and viral diseases. However, the role of CCR5 in diseases caused by bacteria and parasites is still poorly understood. Therefore, the aim of this article is to review the role of CCR5 and the effects of CCR5Δ32 on bacterial (brucellosis, osteomyelitis, pneumonia, tuberculosis and infection by Chlamydia trachomatis) and parasitic infections (toxoplasmosis, leishmaniasis, Chagas disease and schistosomiasis). Basic information about each of these infections was also addressed. The neglected role of CCR5 in fungal disease and emerging studies regarding the action of CCR5 on regulatory T cells are briefly covered in this review. Considering the “renaissance of CCR5 research,” this article is useful for updating researchers who develop studies involving CCR5 and CCR5Δ32 in different infectious diseases.

Maraviroc, celastrol and azelastine alter Chlamydia trachomatis development in HeLa cells

“…Mara, at all tested concentrations, did not have a negative impact on cell metabolism/viability or cell numbers, which is in line with the excellent safety profile of this FDA-approved CCR5 receptor antagonist [17, 18]. The CCR5 receptor (chemokine C-C motif receptor 5) is mainly expressed on inflammatory cells such as T-cells, macrophages and monocytes [18, 37, 38], facilitating chemotaxis of these cells during inflammation [37]. However, other cell types also express this receptor [38], as demonstrated for HeLa cells in vitro [38–40].…”

“…However, other cell types also express this receptor [38], as demonstrated for HeLa cells in vitro [38–40]. The CCR5 receptor is an important co-receptor for the human immunodeficiency virus (HIV), but further plays a complex role in immune-mediated diseases such as multiple sclerosis or transplantation reactions, as well in immune defence against a number of pathogens, including Ct [38, 41, 42]. The chemokine CCL5 (also called RANTES) is one of the main CCR5 ligands [17, 37].…”

“…The CCR5 receptor (chemokine C-C motif receptor 5) is mainly expressed on inflammatory cells such as T-cells, macrophages and monocytes [18, 37, 38], facilitating chemotaxis of these cells during inflammation [37]. However, other cell types also express this receptor [38], as demonstrated for HeLa cells in vitro [38–40]. The CCR5 receptor is an important co-receptor for the human immunodeficiency virus (HIV), but further plays a complex role in immune-mediated diseases such as multiple sclerosis or transplantation reactions, as well in immune defence against a number of pathogens, including Ct [38, 41, 42].…”

Chemokine receptor gene polymorphisms and COVID-19: Could knowledge gained from HIV/AIDS be important?

“…Data suggest that there are varied impacts of CCR5 regulation and CCR5 Δ32 on human infections caused by the following non-HIV viruses: West Nile virus, Tick-borne encephalitis virus, Influenza virus, Human papillomavirus, Hepatitis B virus, Hepatitis C virus, Poliovirus, Dengue virus, Human cytomegalovirus, Crimean-Congo hemorrhagic fever virus, Enterovirus, Japanese encephalitis virus, and Hantavirus ( Klein, 2008 ; Qidwai and Khan, 2016 ; Ellwanger et al, 2020a ). The role of CCR5 in bacterial, parasitic, and fungal diseases has not been much studied ( Klein, 2008 ; Qidwai and Khan, 2016 ; Ellwanger et al, 2020b ).…”

“…As CCR5 is a primary entry receptor for HIV, it is appreciable that expression variations of CCR5 due to CCR5 polymorphisms may influence the acquisition of HIV infection as well as the disease progression. However, the impacts of CCR5 polymorphisms on the replication and infection of non-HIV viruses and other pathogens are complex and may not be generalized ( Klein, 2008 ; Qidwai and Khan, 2016 ; Ellwanger et al, 2020a ; Ellwanger et al, 2020b ). These impacts could be disease-specific and/or population-specific.…”