Abstract
BackgroundThe immune response during P. falciparum infection is a two-edged sword, involving dysregulation of the inflammatory responses with several types of immune cells participating. Here we examined T-cell, monocyte/macrophage and neutrophil activation during P. falciparum infection by using soluble activation markers for these leukocyte subsets.MethodsIn a prospective cross-sectional study clinical data and blood samples were collected from adults in Mozambique with P. falciparum infection, with (n = 70) and without (n = 61) co-infection with HIV-1, as well as HIV-infected patients with similar symptoms but without malaria (n = 58) and healthy controls (n = 52). Soluble (s)CD25, sCD14, sCD163 and myeloperoxidase (MPO) as markers for T-cell, monocyte/macrophage and neutrophil activation, respectively as well as CX3CL1, granzyme B and TIM-3 as markers of T-cell subsets and T-cell exhaustion, were analyzed.ResultsAll patient groups had raised levels of activation markers compared with healthy controls. Levels of sCD25 and MPO increased gradually from patient with HIV only to patient with malaria only, with the highest levels in the HIV/malaria group. In the malaria group as a whole, MPO, sCD14 and in particular sCD25 were correlated with disease severity. sCD163, sCD25 and in particular MPO correlated with the degree of parasitemia as assessed by qPCR. Patients with falciparum malaria also had signs of T-cell subset activation (i.e. increased granzyme B and CX3CL1) and T-cell exhaustion as assessed by high levels of TIM-3 particularly in patients co-infected with HIV.ConclusionOur data support a marked immune activation in falciparum malaria involving all major leukocyte subsets with particular enhanced activation of neutrophils and T-cells in patients co-infected with HIV. Our findings also support a link between immune activation and immune exhaustion during falciparum malaria, particularly in relation to T-cell responses in patients co-infected with HIV.
Highlights
The immune response during P. falciparum infection is a two-edged sword, involving dysregulation of the inflammatory responses with several types of immune cells participating
MPO, sCD25, sCD14 and sCD163 in P. falciparum infection with and without HIV infection As can be seen in Fig. 1, all soluble markers of leukocyte activation were markedly increased in all groups of patients (HIV without malaria [n = 58], and malaria with [n = 70] and without [n = 61] HIV) as compared with healthy controls (n = 52)
In HIV-infected patients co-infected with P. falciparum there was a significant decline in MPO, sCD25 and sCD14 levels during follow-up, and for MPO, this was seen for malaria patients without HIV infection
Summary
The immune response during P. falciparum infection is a two-edged sword, involving dysregulation of the inflammatory responses with several types of immune cells participating. We examined T-cell, monocyte/macrophage and neutrophil activation during P. falciparum infection by using soluble activation markers for these leukocyte subsets. Infection with Plasmodium falciparum (P. falciparum) is associated with a marked increase in systemic inflammation Whereas this immune activation could contribute to parasite clearance, an enhanced immune response could contribute to disease progression by promoting tissue damage rather than protection and through induction of Otterdal et al BMC Infectious Diseases (2018) 18:670 contribute to a sustained and harmful inflammation during P. falciparum infection, the anti-inflammatory and pro-resolving M2 macrophages may prevent the development of overt disease. There are several studies on immune activation and inflammation during P. falciparum infection, and some of these have examined T-cells, monocytes/macrophages and neutrophils [9,10,11,12], but the role of these cells during falciparum malaria are far from clear. We examined how HIV infection influenced plasma levels of sCD25, sCD14, sCD163 and MPO in these patients
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