Fish oil supplementation benefits the murine host during the acute phase of a parasitic infection from Trypanosoma cruzi

Abstract

Long-chain omega-3 polyunsaturated fatty acids (LC n-3 PUFA) are known to modulate a variety of immune cell functions. On occasion, this has led to diminished host resistance to certain viral and bacterial infections. Little is known about the impact of n-3 PUFA on host resistance to parasitic infection, however, based on results from a small study conducted more than two decades ago, we hypothesized that providing mice LC n-3 PUFA will diminish host resistance to Trypanosoma cruzi, the parasitic pathogen responsible for Chagas disease. To investigate this, C57BL/6 mice were supplemented by gavage (0.6% v/w) with phosphate-buffered saline, corn oil (CO), or menhaden fish oil (FO, a fat source rich in LC n-3 PUFA) for 15 days prior to T cruzi (Y strain) challenge and throughout the acute phase of infection. FO supplementation was associated with a transient 2-fold greater peak of blood parasitemia at 7 days postinfection (dpi), whereas subsequent cardiac parasitemia was ~60% lower at 12 dpi. FO treatment also ameliorated the leukopenia and thrombocytopenia observed in the early stages of a T cruzi infection. FO supplementation reduced circulating and cardiac nitric oxide at 7 and 12 dpi, respectively. FO supplementation altered ex vivo prostaglandin E and cytokine and chemokine production by splenocytes isolated from uninfected and infected mice. Overall, our results suggest that oral administration of LC n-3 PUFA from FO can have beneficial effects on the host in the early course of a T cruzi infection.

Extracellular Vesicles Shed By Trypanosoma cruzi Potentiate Infection and Elicit Lipid Body Formation and PGE2 Production in Murine Macrophages

“…The heart was fixed in 10% buffered formalin for histological analysis. Spleen cells were cultured with medium or total antigen of T. cruzi (TcAg) as previously described ( 38 ), and the supernatants were stored for the quantification of nitrite, cytokines, and prostaglandin E 2 (PGE 2 ) (Cayman, Ann Arbor, MI, USA). The 12th day after infection was chosen during this phase, NO production is elevated, the cells of the acquired immune response are already activated, and the host response begins to control parasitemia ( 39 – 41 ).…”

Host-Directed Drug Therapies for Neglected Tropical Diseases Caused by Protozoan Parasites

“…A recent study by Otta et al (2018) showed that K777 the extract lead compound induces prominent proinflammatory responses modulation by interleukin -10-positive CD4 + /CD8 + T cells and this contributed to the protection against the Chagas disease. In addition, diet supplementation with fish oil led to increase the resistance to T. cruzi infection through modulating various immunological factors ( Lovo-Martins et al, 2017 ).…”

Omega-3 and omega-6 polyunsaturated fatty acids and their potential therapeutic role in protozoan infections

“…Previous studies demonstrated that ω3 and ω6 PUFAs impacted cellular and innate immunity ( 109 , 110 ). These PUFAs also affected the survival of mice following an experimental T. cruzi infection and showed fewer indications during the acute phase of this parasitic infection ( 111 ). The mechanisms for this protection are shown in Figure 4 .…”

“…During the acute form of T. cruzi infection, the increased level of prostaglandin E2 (PGE2) results in temporary immunosuppression, which leads to decreased production of TNF-α by the host ( 112 ). The immune cells from the omega-PUFAs diet lowered PGE2 amounts and consequently increased the level of TNF-α leading to decreased parasitemia ( 111 ). PGE2, Prostaglandin E2; TXA 2 , thromboxane A2; GM-CSF, Granulocyte-macrophage colony-stimulating factor; TNF-α, Tumor necrosis factor-alpha.…”