Abstract
Macrophages (MΦ) play a key role in the development of the protective immune response against Trypanosoma cruzi infection. To determine the role of MΦ subtypes M1 and M2 in the development of immunity against the Mexican strain of T. cruzi (Ninoa strain), we have analysed in a time course the infection and characterised the M1 and M2 subtypes in two mouse models, BALB/c and C57BL/6. After infection, BALB/c mice developed an increased blood parasite load and the parasites were cleared from the blood one week later than in C57BL/6 mice. However, similar cellular infiltrate and cardiac alterations were observed between BALB/c and C57BL/6 mice. At 36 days, the T. cruzi infection differentially modulated the expression of immune cells, and both the BALB/c and C57BL/6 mice significantly reduced TCD4+ cells. However, BALB/c mice produced significantly more TCD8+ than C57BL/6 mice in the spleen and lymph nodes. Furthermore, BALB/c mice produce significantly more MΦ in the spleen, while C57BL/6 produce similar levels to uninfected mice. The M1 MΦ ratio increased significantly at 3–5 days post-infection (dpi), but then decreased slightly. On the contrary, the M2 MΦ were low at the beginning of the infection, but the proportion of M1 and M2 MΦ at 36 dpi was similar. Importantly, the MΦ subtypes M2c and M2d significantly increased the induction of tissue repair by the end of the acute phase of the infection. These results indicate that the Ninoa strain has developed strategies to modulate the immune response, with fine differences depending on the genetic background of the host.
Highlights
Chagas disease or American trypanosomiasis is a neglected tropical disease historically endemic to continental Latin America, that already affects 6 to 7 million persons worldwide [1,2], with 30,000 new cases reported annually for all forms of transmission.Over 70 million persons are at risk of developing the infection, with 8000 newborns infected during gestation and around 12,000 persons dying every year [3,4]
A recent study reported that susceptible BALB/c mice treated with concanavalinA favours peritoneal M1 MΦ polarisation to increase trypanocide activity, resulting in ameliorated systemic T. cruzi infection [24]. These results demonstrate that M1 induce protection against T. cruzi infection in susceptible BALB/c mice, other studies indicate that M2 regulates the lethal nitric oxide (NO) release during T. cruzi infection, along with anti-inflammatory cytokines produced by Th2 cells, such as IL-10 that promotes protection from fatal acute myocarditis [25]
A rapid rapid and increase was in parasitaemia for 8both mouse strains was observed, and continuous increase in parasitaemia for both mousereached strains was observed, in the BALB/c mice, the blood stream parasites a peak at day 20, while in the C57BL/6
Summary
Chagas disease or American trypanosomiasis is a neglected tropical disease historically endemic to continental Latin America, that already affects 6 to 7 million persons worldwide [1,2], with 30,000 new cases reported annually for all forms of transmission.Over 70 million persons are at risk of developing the infection, with 8000 newborns infected during gestation and around 12,000 persons dying every year [3,4]. Chagas disease or American trypanosomiasis is a neglected tropical disease historically endemic to continental Latin America, that already affects 6 to 7 million persons worldwide [1,2], with 30,000 new cases reported annually for all forms of transmission. Chagas disease is a parasitic, systemic, and chronic infection, which is caused by the hemoflagellate protozoan Trypanosoma cruzi (T. cruzi). Multiple forms of non-vectorial ways have been reported, such as congenital (mother to foetus during pregnancy), oral, blood transfusion, tissue transplantation, or laboratory accidents [5], that are relevant and responsible for the spreading from endemic to non-endemic areas. After 60 days of the initial infection, the parasites are cleared from the blood, followed by a long-term clinical condition that can persist for 2–3 decades, referred as the chronic phase
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