Mammalian cell cultures as models for Mycobacterium tuberculosis-human immunodeficiency virus(HIV) interaction studies:A review

Mycobacterium tuberculosis(MTB) and human immunodeficiency virus(HIV) co-infections have remained a major public health concern worldwide,particularly in Southern Africa.Yet our understanding of the molecular interactions between the pathogens has remained poor,primarily due to lack of suitable preclinical models for such studies.We reviewed the use,this far,of mammalian cell culture models in HIV-MTB interaction studies.Studies have described the use of primary human cell cultures,including monocyte-derived macrophage(MDM) fractions of peripheral blood mononuclear cell(PBMC),alveolar macrophages(AM),cell lines such as the monocyte-derived macrophage cell line(U937),T lymphocyte cell lines(CEMx174,ESAT-6-specific CD4+ T-cells) and an alveolar epithelial cell line(A549) and special models such as stem cells,three dimensional(3D) or organoid cell models [including a blood-brain barrier(BBB) cell model] in HIV-MTB interaction studies.The use of cell cultures from other mammals,including:mouse cell lines [macrophage cell lines RAW 264.7 and J774.2,fibroblast cell lines(NIH 3T3,C3 H clones),embryonic fibroblast cell lines and T-lymphoma cell lines(S1A.TB,TIMI.4 and R1.1)]; rat(T cells:Rat2,RGE,XC and HH16,and alveolar cells:NR8383) and primary guinea pigs derived AMs,in HIV-MTB studies is also described.Given the spectrum of the models available,cell cultures offer great potential for host-HIV-MTB interactions studies.

Monocyte/Macrophage-Mediated Innate Immunity in HIV-1 Infection:From Early Response to Late Dysregulation and Links to Cardiovascular Diseases Onset

Although monocytes and macrophages are key mediators of the innate immune system,the focus has largely been on the role of the adaptive immune system in the context of human immunodeficiency virus(HIV)infection.Thus more attention and research work regarding the innate immune system-especially the role of monocytes and macrophages during early HIV-1 infection-is required.Blood monocytes and tissue macrophages are both susceptible targets of HIV-1 infection,and the early host response can determine whether the nature of the infection becomes pathogenic or not.For example,monocytes and macrophages can contribute to the HIV reservoir and viral persistence,and influence the initiation/extension of immune activation and chronic inflammation.Here the expansion of monocyte subsets(classical,intermediate and non-classical)provide an increased understanding of the crucial role they play in terms of chronic inflammation and also by increasing the risk of coagulation during HIV-1 infection.This review discusses the role of monocytes and macrophages during HIV-1 pathogenesis,starting from the early response to late dysregulation that occurs as a result of persistent immune activation and chronic inflammation.Such changes are also linked to downstream targets such as increased coagulation and the onset of cardiovascular diseases.

Expansion of GARP-Expressing CD4^(+)CD25^(-)FoxP3^(+)T Cells and SATB1Association with Activation and Coagulation in Immune Compromised HIV-1-Infected Individuals in South Africa

Although antiretroviral treatment lowers the burden of human immunodeficiency virus(HIV)-related disease,it does not always result in immunological recovery.This manifests as persistent chronic inflammation,immune activation or exhaustion that can promote the onset of co-morbidities.As the exact function of regulatory T(Treg)cells in HIV remains unclear,this cross-sectional study investigated three expression markers(Forkhead box protein P3[FOXP3],glycoprotein A repetitions predominant[GARP],special AT-rich sequence binding protein 1[SATB1])and compared their expansion between CD4^(+)CD25^(-)and CD4^(+)CD25^(++)T cells.Age-matched study subjects were recruited(Western Cape,South Africa)and sub-divided:HIV-negative subjects(n=12),HIV-positive na(i|")ve treated(n=22),HIV-positive treated based on CD4 count cells/μL(CD4>500 and CD4<500)(n=34)and HIV-treated based on viral load(VL)copies/mL(VL<1000 and VL>1000)(n=34).Markers of immune activation(CD38)and coagulation(CD142)on T cells(CD8)were assessed by flow cytometry together with FOXP3,GARP and SATB1 expression on CD4^(+)CD25^(-)and CD4^(+)CD25^(++)T cells.Plasma levels of interleukin-10(IL-10;anti-inflammatory marker),IL-6(inflammatory marker)and D-dimer(coagulation marker)were assessed.This study revealed three major findings in immuno-compromised patients with virological failure(CD4<500;VL>1000):(1)the expansion of the unconventional Treg cell subset(CD4^(+)CD25^(-)FOXP3^(+))is linked with disease progression markers;(2)increased GARP expression in the CD4^(+)CD25^(-)and CD4^(+)CD25^(++)subsets;and(3)the identification of a strong link between CD4^(+)CD25^(-)SATB1+cells and markers of immune activation(CD8^(+)CD38^(+))and coagulation(CD8^(+)CD142^(+)and D-dimer).