Malaria-Cutaneous Leishmaniasis Co-infection: Influence on Disease Outcomes and Immune Response

Abstract

Malaria and Cutaneous Leishmaniasis (CL) are co-endemic throughout large regions in tropical countries and co-infection may impact the evolution of host-parasite interactions. In the present study, we evaluate Malaria/Leishmaniasis disease outcome, Th1/Th2 cytokine levels and the CD4 and CD8 T-cell profiles in a co-infection murine model (BALB/c) of Plasmodium yoelii 17XNL (Py) and Leishmania amazonensis (La) or L. braziliensis (Lb). Malaria parasitaemia was assessed through blood strains stained with Giemsa. Leishmania lesions were monitored with a digital caliper and parasite loads determined by limiting-dilution assay. Serum levels of IFN-γ, TNF, IL-2, IL-4, IL-6, IL-10, and IL-17 were determined using multiplexed bead assay and expression of CD3, CD4, and CD8 T-cells markers were determined by Flow Cytometry in the thymus, spleens and lymph nodes. Parasitaemia in Lb+Py co-infected group was lower than in Py single-infected group, suggesting a protective effect of Lb co-infection in Malaria progression. In contrast, La+Py co-infection increased parasitaemia, patent infection and induced mortality in non-lethal Malaria infection. Regarding Leishmaniasis, Lb+Py co-infected group presented smaller lesions and less ulceration than Lb single-infected animals. In contrast, La+Py co-infected group presented only a transitory delay on the development of lesions when compared to La single-infected mice. Decreased levels of IFN-γ, TNF, IL-6, and IL-10 were observed in the serum of co-infected groups, demonstrating a modulation of Malaria immune response by Leishmania co-infections. We observed an intense thymic atrophy in Py single-infected and co-infected groups, which recovered earlier in co-infected animals. The CD4 and CD8 T cell profiles in thymus, spleens and lymph nodes did not differ between Py single and co-infected groups, except for a decrease in CD4+CD8+ T cells which also increased faster in co-infected mice. Our results suggest that Py and Leishmania co-infection may change disease outcome. Interestingly Malaria outcome can be altered according to the Leishmania specie involved. Alternatively Malaria infection reduced the severity or delayed the onset of leishmanial lesions. These alterations in Malaria and CL development seem to be closely related with changes in the immune response as demonstrated by alteration in serum cytokine levels and thymus/spleens T cell phenotypes dynamics during infection.

Tegumentary leishmaniasis and coinfections other than HIV

“…Seven experimental studies assessed Plasmodium coinfection and TL [ 53 – 59 ]. In coinfection models of Plasmodium yoelii or Plasmodium berghei together with Leishmania enrietti , L .…”

Joint spatial time-series epidemiological analysis of malaria and cutaneous leishmaniasis infection

“…Moreover, previous studies has found patients suffering from malaria infections exhibit the presence of Leishmania parasites in their body [55] or vice versa [16, 17]. The outcome of malaria infections can be altered according to the Leishmania species involved [19]. When both malaria and leishmaniasis are present in humans, it affects the disease outcome and progression of disease due to the modulation of the immune response [18, 19].…”

“…The outcome of malaria infections can be altered according to the Leishmania species involved [19]. When both malaria and leishmaniasis are present in humans, it affects the disease outcome and progression of disease due to the modulation of the immune response [18, 19].…”

“…The co-existence of multiple pathogens in certain populations as well as their distribution is part of a natural selection, as a result of favourable ecological and host factors, which include the biological interactions of the parasites within the host [16, 17]. The presence of both malaria and leishmaniasis in humans could influence disease outcome and progression of diseases due to the modulation of immune response [16, 18, 19].…”

<b>Genes de cisteíno proteases (catepsina L-like) de <i>Leishmania infantum chagasi</i></b>: caracterização, relações filogenéticas e diagnóstico molecular

“…Em humanos a hipergamaglobulinemia, leucopenia, tosse seca, quadros febris, anemia e hepatoesplenomegalia são as características cardeais da sintomatologia de leishmaniose visceral, sendo que nas situações em que a doença progride acentuadamente podem ser observados episódios de anemia, pancitopenia, emagrecimento progressivo, diarreia, icterícia, vômito e edema periférico, além de eventuais comorbidades infecciosas em pacientes com malária ou portadores do vírus HIV (PASTORINO et al, 2002;DESJEUX e ALVAR, 2003;QUEIROZ et al, 2004;SILVA et al, 2008;OLIVEIRA et al, 2010;LINDOSO et al, 2016;PINNA et al, 2016). LEE et al, 2002;PASCALIS et al, 2003;SILVA-ALMEIDA et al, 2012;AGALLOU et al, 2017).…”