Abstract
BackgroundChronic infection with Trypanosoma cruzi leads to a constant stimulation of the host immune system. Monocytes, which are recruited in response to inflammatory signals, are divided into classical CD14hiCD16—, non-classical CD14loCD16+ and intermediate CD14hiCD16+ subsets. In this study, we evaluated the frequencies of monocyte subsets in the different clinical stages of chronic Chagas disease in comparison with the monocyte profile of seronegative heart failure subjects and seronegative healthy controls. The effect of the anti-parasite drug therapy benznidazole on monocyte subsets was also explored.Methodology/Principal findingsThe frequencies of the different monocyte subsets and their phenotypes were measured by flow cytometry. Trypanosoma cruzi-specific antibodies were quantified by conventional serological tests. T. cruzi-infected subjects with mild or no signs of cardiac disease and patients suffering from dilated cardiomyopathy unrelated to T. cruzi infection showed increased levels of non-classical CD14loCD16+ monocytes compared with healthy controls. In contrast, the monocyte profile in T. cruzi-infected subjects with severe cardiomyopathy was skewed towards the classical and intermediate subsets. After benznidazole treatment, non-classical monocytes CD14loCD16+ decreased while classical monocytes CD14hiCD16—increased.Conclusions/SignificanceThe different clinical stages of chronic Chagas disease display distinct monocyte profiles that are restored after anti-parasite drug therapy. T. cruzi-infected subjects with severe cardiac disease displayed a profile of monocytes subsets suggestive of a more pronounced inflammatory environment compared with subjects suffering from heart failure not related to T. cruzi infection, supporting that parasite persistence might also alter cell components of the innate immune system.
Highlights
Chagas disease, caused by infection with the intracellular protozoan parasite Trypanosoma cruzi, affects 6–7 million people and represents the most frequent cause of infectious cardiomyopathy in the world [1,2]
Because chronic T. cruzi infection induces a constant activation of the host immune system, inflammatory signals are exacerbated, possibly leading to alterations in the frequencies of monocyte subsets
We evaluated the monocyte profile in Trypanosoma cruzi-infected subjects with different degrees of cardiac dysfunction and explored whether this profile was similar between seropositive and seronegative subjects with heart failure
Summary
Chagas disease, caused by infection with the intracellular protozoan parasite Trypanosoma cruzi, affects 6–7 million people and represents the most frequent cause of infectious cardiomyopathy in the world [1,2]. In response to inflammatory signals, circulating monocytes leave the bloodstream and migrate into tissues, where following conditioning by local growth factors, pro-inflammatory cytokines and microbial products, they differentiate into macrophages or dendritic cells. CD14hiCD16−monocytes “classical Mo”, which are referred to as classical monocytes, are the most prevalent monocyte subset in human blood, and they show a high expression of the chemokine receptor CCR2. Classical monocytes can migrate to sites of injury and infection, where they differentiate into inflammatory macrophages [5]. The CD16+ monocyte population comprises two subsets: the non-classical CD14loCD16+ “non-classical Mo” and the intermediate CD14hiCD16+ monocytes “intermediate Mo” [4,6]. Both subsets exhibit low and mild CCR2 expression [7]. Whereas non-classical monocytes are involved in the process of patrolling with potent anti-inflammatory function and wound healing, intermediate monocytes share some phenotypic and functional features of both classical and non-classical monocytes
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