Co‐infection with distinct Trypanosoma cruzi strains induces an activated immune response in human monocytes

Abstract

Aims The aim of the study was to evaluate the immune response triggered by the first contact of human monocytes with two T cruzi strains from distinct discrete typing units (DTUs) IV and V, and whether co‐infection with these strains leads to changes in monocyte immune profiles, which could in turn influence the subsequent infection outcome. Methods and results We evaluated the influence of in vitro single‐ and co‐infection with AM64 and 3253 strains on immunological characteristics of human monocytes. Single infection of monocytes with AM64 or 3253 induced opposing anti‐inflammatory and inflammatory responses, respectively. Co‐infection was observed in over 50% of monocytes after 15 hours of culture, but this percentage dropped ten‐fold after 72 hours. Co‐infection led to high monocyte activation and an increased percentage of both IL‐10 and TNF. The decreased percentage of co‐infected cells observed after 72 hours was associated with a decreased frequency of TNF‐expressing cells. Conclusion Our results show that the exacerbated response observed in co‐infection with immune‐polarizing strains is associated with a decreased frequency of co‐infected cells, suggesting that the activated response favours parasite control. These findings may have implications for designing new Chagas disease preventive strategies.

Landmarks of the Knowledge and Trypanosoma cruzi Biology in the Wild Environment

“…Mixed infection is a topic that has been receiving increasing attention due to the possible impacts on the host. Concerning genotypes of T. cruzi, Magalhães and coauthors evaluated the impact of T. cruzi DTUs TcIV and TcV on human monocytes (Magalhães et al, 2019). The authors observed that unlike single infections, coinfections resulted in increased expression of IL10 and TNF, which led the authors to conclude that mixed infection has the potential to favor parasite control.…”

New insights into Trypanosoma cruzi genetic diversity, and its influence on parasite biology and clinical outcomes

“…Differences in the capacity of T. cruzi for cell penetration, infectivity, differential induction of the immune response, tissue tropism, and response to treatment have already been demonstrated ( 84 – 86 ), which could confer differential capacity for adaptation to the host, influencing the transmission, response to the treatment, and the course of the infection ( 5 , 87 ). Several studies have also demonstrated that distinct T. cruzi strains could trigger different immune responses and be influenced by geographical location ( 31 , 88 – 93 ).…”

“…Distinct T. cruzi DTUs may exhibit variations in parasitemia, immune responses, and tissue pathology in their hosts ( 89 – 91 , 93 ). Moreover, these parameters may differ in co-infections compared to T. cruzi mono-infections ( 89 ).…”

Pathogen diversity, immunity, and the fate of infections: lessons learned from Trypanosoma cruzi human–host interactions

“…59 Evaluating the response of human monocytes to AM-64 strain (TcIV) or 3253 strain (TcV) isolates, we observed that they induced opposing anti-inflammatory and highly inflammatory profiles, respectively. 60 An association between TcI or TcII single infection and TcI and TcII co-infection, and different concentrations of circulating cytokines, was evaluated in patients with chronic Chagas disease from Bolivia and Colombia. 61 Although an inflammatory profile was observed in all groups, no particular pattern was associated with the different DTUs.…”