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Unravelling the patterns of host immune responses in Plasmodium vivax malaria and dengue co-infection.

Mendonça VR, Andrade BB, Souza LC, Magalhães BM, Mourão MP, Lacerda MV, Barral-Netto M - Malar. J. (2015)

Bottom Line: The plasma levels of cytokines and chemokines were determined by multiplex assay.The group of individuals co-infected exhibited the highest median concentrations of IFN-γ, IL-6, CCL4 than the mono-infected groups.Further, parasitaemia levels displayed positive significant interactions with IL-6, CCL4 and IL-10 in the group of patients co-infected with malaria and dengue.

View Article: PubMed Central - PubMed

Affiliation: Laboratório Integrado de Microbiogia e Imunoregulação (LIMI), Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz (FIOCRUZ), Salvador, Brazil. vitorrosaramos@hotmail.com.

ABSTRACT

Background: Concurrent malaria and dengue infection is frequently diagnosed in endemic countries, but its immunopathology remains largely unknown. In the present study, a large panel of cytokines/chemokines and clinical laboratory markers were measured in patients with Plasmodium vivax and dengue co-infection as well as in individuals with malaria or dengue mono-infections in order to identify biosignatures of each clinical condition.

Methods: Individuals from the Brazilian Amazon were recruited between 2009 and 2013 and classified in three groups: vivax malaria (n = 52), dengue (n = 30) and vivax malaria and dengue co-infection (n = 30). P. vivax malaria was diagnosed by thick blood smear and confirmed by PCR; dengue cases were detected by IgM ELISA or NS1 protein. The plasma levels of cytokines and chemokines were determined by multiplex assay.

Results: Individuals with malaria and dengue co-infection displayed lower levels of platelets and haemoglobin than those with malaria or dengue mono-infections (p = 0.0047 and p = 0.0001, respectively). The group of individuals co-infected exhibited the highest median concentrations of IFN-γ, IL-6, CCL4 than the mono-infected groups. Network analyses of plasma cytokines/chemokines revealed that malaria and dengue co-infection exhibits a distinct immune profile with critical roles for TNF, IL-6 and IFN-γ. Further, parasitaemia levels displayed positive significant interactions with IL-6, CCL4 and IL-10 in the group of patients co-infected with malaria and dengue. No differences were observed in distribution of dengue virus serotypes and Plasmodium parasitaemia levels between the groups.

Conclusions: The findings described here identify unique patterns of circulating immunological markers in cases of malaria and dengue co-infection and provide insights on the immunopathology of this co-morbid condition.

No MeSH data available.


Related in: MedlinePlus

Associations between laboratory parameters, parasitaemia and immune-related biomarkers. Statistically significant correlations between laboratory markers (a) or parasitaemia (b) and immune-related biomarkers are shown for the different groups. The correlations were assessed using the Spearman rank test. The interactions involving parasitaemia shown in (c) are plotted on top of the host interactome. Green lines represent negative significant (P < 0.05) correlations and orange lines, positive significant correlations.
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Fig3: Associations between laboratory parameters, parasitaemia and immune-related biomarkers. Statistically significant correlations between laboratory markers (a) or parasitaemia (b) and immune-related biomarkers are shown for the different groups. The correlations were assessed using the Spearman rank test. The interactions involving parasitaemia shown in (c) are plotted on top of the host interactome. Green lines represent negative significant (P < 0.05) correlations and orange lines, positive significant correlations.

Mentions: The next step was to uncover the interactions between clinical laboratory markers and the immune-related molecules. In all the study groups, HB exhibited positive associations with HT whereas ALT exhibited positive correlations with AST (Fig. 3a). It was found that HB and HT displayed several negative significant interactions mainly with IL-4, IL-5, IL-12p70, and IL-17, whereas ALT interacted negatively with IL-4 and IL-7 in the malaria group (Fig. 3a). In the group of patients with malaria and dengue co-infection, HB and HT displayed negative associations with IL-7, whereas AST exhibited positive interactions with CCL2, IL-13 and IL-8 (Fig. 3a). Noteworthy, it was observed that only in the dengue mono-infection group did PTL display interactions with immune markers (positive interactions with GMCSF, GCSF and IL-8), suggesting a major role for this molecule in this group (Fig. 3a). Furthermore, AST and ALT displayed negative associations with TNF in the network of the dengue mono-infection group (Fig. 3a). In the P. vivax-infected groups, the associations between parasitaemia and the immune markers were also studied (Fig. 3b). It was observed that P. vivax parasitaemia displayed positive significant interactions with IL-6, CCL4 and IL-10 in the group of patients co-infected with malaria and dengue, while this parameter exhibited several positive correlations with many immune markers (GCSF, CCL2, CCL4, TNF, IL-12p70, IL-10, IL-6, and IL-4) in the group of malaria mono-infected subjects, suggesting a major role for parasitaemia in the immune profile in this clinical condition (Fig. 3b). P values and Spearman rank values for each correlation between the immune biomarkers and laboratory measures or parasitaemia are provided (see Additional file 3).Fig. 3


Unravelling the patterns of host immune responses in Plasmodium vivax malaria and dengue co-infection.

Mendonça VR, Andrade BB, Souza LC, Magalhães BM, Mourão MP, Lacerda MV, Barral-Netto M - Malar. J. (2015)

Associations between laboratory parameters, parasitaemia and immune-related biomarkers. Statistically significant correlations between laboratory markers (a) or parasitaemia (b) and immune-related biomarkers are shown for the different groups. The correlations were assessed using the Spearman rank test. The interactions involving parasitaemia shown in (c) are plotted on top of the host interactome. Green lines represent negative significant (P < 0.05) correlations and orange lines, positive significant correlations.
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4536664&req=5

Fig3: Associations between laboratory parameters, parasitaemia and immune-related biomarkers. Statistically significant correlations between laboratory markers (a) or parasitaemia (b) and immune-related biomarkers are shown for the different groups. The correlations were assessed using the Spearman rank test. The interactions involving parasitaemia shown in (c) are plotted on top of the host interactome. Green lines represent negative significant (P < 0.05) correlations and orange lines, positive significant correlations.
Mentions: The next step was to uncover the interactions between clinical laboratory markers and the immune-related molecules. In all the study groups, HB exhibited positive associations with HT whereas ALT exhibited positive correlations with AST (Fig. 3a). It was found that HB and HT displayed several negative significant interactions mainly with IL-4, IL-5, IL-12p70, and IL-17, whereas ALT interacted negatively with IL-4 and IL-7 in the malaria group (Fig. 3a). In the group of patients with malaria and dengue co-infection, HB and HT displayed negative associations with IL-7, whereas AST exhibited positive interactions with CCL2, IL-13 and IL-8 (Fig. 3a). Noteworthy, it was observed that only in the dengue mono-infection group did PTL display interactions with immune markers (positive interactions with GMCSF, GCSF and IL-8), suggesting a major role for this molecule in this group (Fig. 3a). Furthermore, AST and ALT displayed negative associations with TNF in the network of the dengue mono-infection group (Fig. 3a). In the P. vivax-infected groups, the associations between parasitaemia and the immune markers were also studied (Fig. 3b). It was observed that P. vivax parasitaemia displayed positive significant interactions with IL-6, CCL4 and IL-10 in the group of patients co-infected with malaria and dengue, while this parameter exhibited several positive correlations with many immune markers (GCSF, CCL2, CCL4, TNF, IL-12p70, IL-10, IL-6, and IL-4) in the group of malaria mono-infected subjects, suggesting a major role for parasitaemia in the immune profile in this clinical condition (Fig. 3b). P values and Spearman rank values for each correlation between the immune biomarkers and laboratory measures or parasitaemia are provided (see Additional file 3).Fig. 3

Bottom Line: The plasma levels of cytokines and chemokines were determined by multiplex assay.The group of individuals co-infected exhibited the highest median concentrations of IFN-γ, IL-6, CCL4 than the mono-infected groups.Further, parasitaemia levels displayed positive significant interactions with IL-6, CCL4 and IL-10 in the group of patients co-infected with malaria and dengue.

View Article: PubMed Central - PubMed

Affiliation: Laboratório Integrado de Microbiogia e Imunoregulação (LIMI), Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz (FIOCRUZ), Salvador, Brazil. vitorrosaramos@hotmail.com.

ABSTRACT

Background: Concurrent malaria and dengue infection is frequently diagnosed in endemic countries, but its immunopathology remains largely unknown. In the present study, a large panel of cytokines/chemokines and clinical laboratory markers were measured in patients with Plasmodium vivax and dengue co-infection as well as in individuals with malaria or dengue mono-infections in order to identify biosignatures of each clinical condition.

Methods: Individuals from the Brazilian Amazon were recruited between 2009 and 2013 and classified in three groups: vivax malaria (n = 52), dengue (n = 30) and vivax malaria and dengue co-infection (n = 30). P. vivax malaria was diagnosed by thick blood smear and confirmed by PCR; dengue cases were detected by IgM ELISA or NS1 protein. The plasma levels of cytokines and chemokines were determined by multiplex assay.

Results: Individuals with malaria and dengue co-infection displayed lower levels of platelets and haemoglobin than those with malaria or dengue mono-infections (p = 0.0047 and p = 0.0001, respectively). The group of individuals co-infected exhibited the highest median concentrations of IFN-γ, IL-6, CCL4 than the mono-infected groups. Network analyses of plasma cytokines/chemokines revealed that malaria and dengue co-infection exhibits a distinct immune profile with critical roles for TNF, IL-6 and IFN-γ. Further, parasitaemia levels displayed positive significant interactions with IL-6, CCL4 and IL-10 in the group of patients co-infected with malaria and dengue. No differences were observed in distribution of dengue virus serotypes and Plasmodium parasitaemia levels between the groups.

Conclusions: The findings described here identify unique patterns of circulating immunological markers in cases of malaria and dengue co-infection and provide insights on the immunopathology of this co-morbid condition.

No MeSH data available.


Related in: MedlinePlus