BALB/c and C57BL/6 Mice Cytokine Responses to Trypanosoma cruzi Infection Are Independent of Parasite Strain Infectivity

Abstract

Trypanosoma cruzi is the etiologic agent of Chagas’ disease, which affects 6–7 million people worldwide. Different strains of T. cruzi present specific genotypic and phenotypic characteristics that affect the host–pathogen interactions, and thus, the parasite has been classified into six groups (TcI to TcVI). T. cruzi infection presents two clinical phases, acute and chronic, both with distinct characteristics and important participation by the immune system. However, the specific contributions of parasite and host factors in the disease phases are not yet fully understood. The murine model for Chagas’ disease is well-established and reproduces important features of the human infection, providing an experimental basis for the study of host lineages and parasite strains. Thus, we evaluated acute and chronic infection by the G (TcI) and CL (TcVI) strains of T. cruzi, which have distinct tropisms and infectivity, in two inbred mice lineages (C57BL/6 and BALB/c) that display variable degrees of susceptibility to different T. cruzi strains. Analysis of the parasite loads in host tissues by qPCR showed that CL strain established an infection faster than the G strain; at the same time, the response in BALB/c mice, although diverse in terms of cytokine secretion, was initiated earlier than that in C57BL/6 mice. At the parasitemia peak in the acute phase, we observed, either by confocal microscopy or by qPCR, that the infection was disseminated in all groups analyzed, with some differences concerning parasite tropism; at this point, all animals responded to infection by increasing the serum concentrations of cytokines. However, BALB/c mice seemed to better regulate the immune response than C57BL/6 mice. Indeed, in the chronic phase, C57BL/6 mice still presented exacerbated cytokine and chemokine responses. In summary, our results indicate that in these experimental models, the deregulation of immune response that is typical of chronic Chagas’ disease may be due to control loss over pro- and anti-inflammatory cytokines early in the acute phase of the disease, depending primarily on the host background rather than the parasite strain.

Trypanosoma cruziMexican Strains Differentially Modulate Surface Markers and Cytokine Production in Bone Marrow-Derived Dendritic Cells from C57BL/6 and BALB/c Mice

“…These different results using the same strains show that in addition to the parasite genetics, the infected cell line and the immune response caused by the contact of the parasite with the cell are associated with the infection. Additionally, the cells derived from the C57B/6 and BALB/c mice present different degrees of susceptibility and/or resistance [51]. Our results show that the Ninoa strain has a higher infectivity potential when the BMDCs are activated with LPS, while the CL-Brener strain is more infective in BMDCs not yet activated.…”

“…Our data showed that all three strains infected DCs efficiently. However, strains belonging to the TcI genotype (AQ1.7, Mutum, and G) presented a profile with low infectivity in BMDCs [6, 51]. This can be explained by the fact that T. cruzi presents a high intraspecific genetic and phenotypic diversity, especially for the TcI genotype.…”

“…In BMDC from BALB/c mice, the Ninoa strain lead to a reduction in IL-6 and an increase in IL-10 production, while in C57BL/6 mice the cytokine production was associated with a huge increment in TNF- α and IL-10. Cytokines are one of the most relevant factors in determining the course of infection [17, 51, 58]. During the process of infection by T. cruzi , a modulating response associated with susceptibility to the disease can be triggered by the parasite.…”

Comparative analysis of thymic subpopulations during different modes of atrophy identifies the reactive oxygen species scavenger, N‐acetyl cysteine, to increase the survival of thymocytes during infection‐induced and lipopolysaccharide‐induced thymic atrophy

“…Also, there is a delay in the differentiation process of SPs and CD24 hi SPs accumulate in both CD4 + and CD8 + SP compartments, which is primarily dependent on infection‐induced IFN‐ γ . However, BALB/c mice are less inflammatory compared with C57BL/6 mice, display reduced thymic atrophy and mice survival on a comparative basis. It is likely that the lower accumulation of CD24 hi SPs may be due to the comparatively reduced amounts of infection‐induced IFN‐ γ produced in BALB/c mice.…”

Advances in understanding the role of adipose tissue and mitochondrial oxidative stress in Trypanosoma cruzi infection

“…Levels of TNFα, IFNγ, and IL-1β in the adipose tissue of chronically infected CD1 mice significantly increased at 90 days after infection 7 . Serum levels of several cytokines and chemokines (TNFα, IL-1β, IL-4, IL-5, CCL-5, CCL-11, CXCL-9, IL-2, IL-10, IL-17, and CCL-3) also increased during chronic infection in C57BL/6 mice (depending on the strain of T. cruzi ) 25, 26 . These levels of serum pro-inflammatory markers subside during the indeterminate stage and then increase during chronic stages in T. cruzi –infected humans with cardiac abnormalities 27, 28 .…”