Cytokine Gene Expression Profiles during HIV and Helminth Coinfection in Underprivileged Peri-Urban South African Adults.

BACKGROUND: Intestinal helminth parasites are potent stimulators of T helper type 2 (Th2) and regulatory Th3 anti-inflammatory immune responses, while human immunodeficiency virus (HIV) infections are activators of predominantly T helper type 1(Th1) pro-inflammatory responses. Studies investigating the immune profiles of individuals coinfected with helminths and HIV are scarce. Although it is well known that helminths cause a type 2 immune response during the chronic stage of infection that is characterised by Th2 cell differentiation, eosinophil recruitment, and alternative macrophage activation, the immune mechanisms that regulate tissue damage at the time of parasite invasion are poorly understood. AIM: The aim of the study was to determine the cytokine gene expression profiles during HIV and helminth coinfection in underprivileged South African adults living in a peri-urban area with poor sanitary conditions and a lack of clean water supply. METHOD: Study participants (n = 164) were subdivided into uninfected controls, HIV-infected, helminth-infected, and HIV and helminth-coinfected groups. The Kato-Katz and Mini Parasep techniques and Ascaris lumbricoides-specific Immunoglobulin E (IgE) and Immunoglobulin G4 (IgG4) levels were used to detect helminth infections. Participants' HIV status was determined using two HIV1/2 antibody test kits. RNA was isolated from white blood cells for cytokine (Th1-, Th2-, and Th17-related) and transcription factor gene expression profiling using real-time PCR. RESULTS: Multivariate regression data were adjusted for age, gender, BMI, antiretroviral treatment (ART), and nutritional supplement intake. The HIV and helminth-coinfected group had significantly higher tumour necrosis factor alpha (TNF-α) (adjusted ß = 0.53, p = 0.036), interleukin 2 (IL-2) (adjusted ß = 6.48, p = 0.008), and interleukin 17 (IL-17) (adjusted ß = 1.16, p = 0.001) levels and lower GATA binding protein 3 (GATA3) levels (adjusted ß = -0.77, p = 0.018) compared to the uninfected controls. No statistical significance was noted for Th2-related cytokines. CONCLUSION: The coinfected group had higher proinflammatory Th1- and Th17-related cytokine gene expression profiles compared to the uninfected controls. The findings suggest that pro-inflammatory responses are elevated during coinfection, which supports the hypothesis that helminths have a deleterious effect on HIV immune responses.

Cytokine Responses during Mycobacterium tuberculosis H37Rv and Ascaris lumbricoides Costimulation Using Human THP-1 and Jurkat Cells, and a Pilot Human Tuberculosis and Helminth Coinfection Study.

BACKGROUND: Helminth infections are widespread in tuberculosis-endemic areas and are associated with an increased risk of active tuberculosis. In contrast to the pro-inflammatory Th1 responses elicited by Mycobacterium tuberculosis (Mtb) infection, helminth infections induce anti-inflammatory Th2/Treg responses. A robust Th2 response has been linked to reduced tuberculosis protection. Several studies show the effect of helminth infection on BCG vaccination and TB, but the mechanisms remain unclear. AIM: To determine the cytokine response profiles during tuberculosis and intestinal helminth coinfection. METHODS: For the in vitro study, lymphocytic Jurkat and monocytic THP-1 cell lines were stimulated with Mtb H37Rv and Ascaris lumbricoides (A. lumbricoides) excretory-secretory protein extracts for 24 and 48 h. The pilot human ex vivo study consisted of participants infected with Mtb, helminths, or coinfected with both Mtb and helminths. Thereafter, the gene transcription levels of IFN-γ, TNF-α, granzyme B, perforin, IL-2, IL-17, NFATC2, Eomesodermin, IL-4, IL-5, IL-10, TGF-ß and FoxP3 in the unstimulated/uninfected controls, singly stimulated/infected and costimulated/coinfected groups were determined using RT-qPCR. RESULTS: TB-stimulated Jurkat cells had significantly higher levels of IFN-γ, TNF-α, granzyme B, and perforin compared to unstimulated controls, LPS- and A. lumbricoides-stimulated cells, and A. lumbricoides plus TB-costimulated cells (p < 0.0001). IL-2, IL-17, Eomes, and NFATC2 levels were also higher in TB-stimulated Jurkat cells (p < 0.0001). Jurkat and THP-1 cells singly stimulated with TB had lower IL-5 and IL-4 levels compared to those singly stimulated with A. lumbricoides and those costimulated with TB plus A. lumbricoides (p < 0.0001). A. lumbricoides-singly stimulated cells had higher IL-4 levels compared to TB plus A. lumbricoides-costimulated Jurkat and THP-1 cells (p < 0.0001). TGF-ß levels were also lower in TB-singly stimulated cells compared to TB plus A. lumbricoides-costimulated cells (p < 0.0001). IL-10 levels were lower in TB-stimulated Jurkat and THP-1 cells compared to TB plus A. lumbricoides-costimulated cells (p < 0.0001). Similar results were noted for the human ex vivo study, albeit with a smaller sample size. CONCLUSIONS: Data suggest that helminths induce a predominant Th2/Treg response which may downregulate critical Th1 responses that are crucial for tuberculosis protection.

The challenges of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing in low-middle income countries and possible cost-effective measures in resource-limited settings.

Diagnostic testing for the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection remains a challenge around the world, especially in low-middle-income countries (LMICs) with poor socio-economic backgrounds. From the beginning of the pandemic in December 2019 to August 2021, a total of approximately 3.4 billion tests were performed globally. The majority of these tests were restricted to high income countries. Reagents for diagnostic testing became a premium, LMICs either cannot afford or find manufacturers unwilling to supply them with expensive analytical reagents and equipment. From March to December 2020 obtaining testing kits for SARS-CoV-2 testing was a challenge. As the number of SARS-CoV-2 infection cases increases globally, large-scale testing still remains a challenge in LMICs. The aim of this review paper is to compare the total number and frequencies of SARS-CoV-2 testing in LMICs and high-income countries (HICs) using publicly available data from Worldometer COVID-19, as well as discussing possible interventions and cost-effective measures to increase testing capability in LMICs. In summary, HICs conducted more SARS-CoV-2 testing (USA: 192%, Australia: 146%, Switzerland: 124% and Canada: 113%) compared to middle-income countries (MICs) (Vietnam: 43%, South Africa: 29%, Brazil: 27% and Venezuela: 12%) and low-income countries (LICs) (Bangladesh: 6%, Uganda: 4% and Nigeria: 1%). Some of the cost-effective solutions to counteract the aforementioned problems includes using saliva instead of oropharyngeal or nasopharyngeal swabs, sample pooling, and testing high-priority groups to increase the number of mass testing in LMICs.

SARS-CoV-2 and helminth co-infections, and environmental pollution exposure: An epidemiological and immunological perspective.

Soil-transmitted helminths infect billions of people globally, particularly those residing in low- and middle-income regions with poor environmental sanitation and high levels of air and water pollution. Helminths display potent immunomodulatory activity by activating T helper type 2 (Th2) anti-inflammatory and Th3 regulatory immune responses. The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the virus that causes Coronavirus disease 2019 (COVID-19), can exacerbate Th1/Th17 pro-inflammatory cytokine production in humans, leading to a cytokine storm. Air pollutants (particulate matter, oxygen radicals, hydrocarbons and volatile organic compounds) and water pollutants (metals and organic chemicals) can also intensify Th1/Th17 immune response and could exacerbate SARS-CoV-2 related respiratory distress and failure. The present review focused on the epidemiology of SARS-CoV-2, helminths and fine particulate matter 2.5 µm or less in diameter (PM2.5) air pollution exposure in helminth endemic regions, the possible immunomodulatory activity of helminths against SARS-CoV-2 hyper-inflammatory immune response, and whether air and water pollutants can further exacerbate SARS-CoV-2 related cytokine storm and in the process hinder helminths immunomodulatory functionality. Helminth Th2/Th3 immune response is associated with reductions in lung inflammation and damage, and decreased expression levels of angiotensin-converting enzyme 2 (ACE2) receptors (SARS-CoV-2 uses the ACE2 receptors to infect cells and associated with extensive lung damage). However, air pollutants are associated with overexpression of ACE2 receptors in the epithelial cell surface of the respiratory tract and exhaustion of Th2 immune response. Helminth-induced immunosuppression activity reduces vaccination efficacy, and diminishes vital Th1 cytokine production immune responses that are crucial for combating early stage infections. This could be reversed by continuous air pollution exposure which is known to intensify Th1 pro-inflammatory cytokine production to a point where the immunosuppressive activities of helminths could be hindered. Again, suppressed activities of helminths can also be disadvantageous against SARS-CoV-2 inflammatory response. This "yin and yang" approach seems complex and requires more understanding. Further studies are warranted in a cohort of SARS-CoV-2 infected individuals residing in helminths and air pollution endemic regions to offer more insights, and to impact mass periodic deworming programmes and environmental health policies.