Characterisation of Macrophage Polarisation in Mice Infected with Ninoa Strain of Trypanosoma cruzi

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.

Statins change the cytokine profile in Trypanosoma cruzi-infected U937 macrophages and murine cardiac tissue through Rho-associated kinases inhibition

“…Lymphocytes and macrophages from patients with CCC secrete higher levels of pro-inflammatory cytokines than asymptomatic chronic Chagasic patients ( 11 ); thus, reducing the pro-inflammatory environment is a promising pharmacological strategy in CCC. Although in in vivo models of the acute CD there is an increase in M1 and M2 cytokines ( 56 ), in vitro models have mainly reported an increase in M1 cytokines ( 57 , 58 ). Nevertheless, our results evidenced an increase of both M1 and M2 markers induced by T. cruzi in vitro , as reported by Mendonça et al.…”

Sensor Array-Enabled Identification of Drugs for Repolarization of Macrophages to Anti-Inflammatory Phenotypes

“…16 For example, M2a is also called wound healing macrophages, and repolarization of M1 to M2a is involved in allergic response 17 and the killing of parasites. 18 M2b is the key subtype to regulate the proliferative phase of repair, 19 and M2b repolarization is predominantly responsible for tissue repair and remodeling. 20 M2c repolarization is associated with immunosuppression, 21 phagocytosis, 22 besides tissue remodeling.…”

“…M2 macrophages display different phenotypes (M2a, M2b, and M2c) depending on the activating stimulus and resulting surface biomarker expression, and these subtypes differ in their biological functions . For example, M2a is also called wound healing macrophages, and repolarization of M1 to M2a is involved in allergic response and the killing of parasites . M2b is the key subtype to regulate the proliferative phase of repair, and M2b repolarization is predominantly responsible for tissue repair and remodeling .…”

Advances in the Immunobiology of Parasitic Diseases

“…Thus, a part of this Special Issue is focused on new advances in immune cell effectors and new immune players on immunomodulation in several parasitic infections. To start this section, an essential player in innate immunity was studied by Medina-Buelvas et al [ 5 ], who assessed a role of macrophages (MΦ). They propose that this cell type plays a crucial role in developing the protective immune response against Trypanosoma cruzi infection.…”