Events associated with susceptibility to invasive Salmonella enterica serovar Typhi in BALB/c mice previously infected with Plasmodium berghei ANKA.

Numerous mechanisms have been proposed to explain why patients with malaria are more susceptible to bloodstream invasions by Salmonella spp., however there are still several unknown critical factors regarding the pathogenesis of coinfection. From a coinfection model, in which an S. enterica serovar Typhi (S_Typhi) was chosen to challenge mice that had been infected 24 h earlier with Plasmodium berghei ANKA (P.b_ANKA), we evaluated the influence of malaria on cytokine levels, the functional activity of femoral bone marrow-derived macrophages and neutrophils, and intestinal permeability. The cytokine profile over eight days of coinfection showed exacerbation in the cytokines MCP-1, IFNγ and TNFα in relation to the increase seen in animals with malaria. The cytokine profile was associated with a considerably reduced neutrophil and macrophage count and a prominent dysfunction, especially in ex vivo neutrophils in coinfected mice, though without bacterial modulation that could influence the invasion capacity of ex vivo S_Typhi obtained from liver macerate in non-phagocyte cells. Finally, irregularities in the integrity of intestinal tissue evidenced ruptures in the enterocyte layer, a presence of mononuclear leukocytes in the enterocyte layer, an increase of goblet cells in the enterocyte layer and a high volume of leukocyte infiltrate in the sub-mucosa were greatly increased in coinfected animals. Increases of mononuclear leukocytes in the enterocyte layer and volume of leukocyte infiltrate in the sub-mucosa were also seen in monoinfected animals with P. berghei ANKA. Our findings suggest malaria causes a disarrangement of intestinal homeostasis, exacerbation of proinflammatory cytokines and dysfunction in neutrophils that render the host susceptible to bacteremia by Salmonella spp.

What are the immune responses during the growth of Ehrlich's tumor in ascitic and solid form?

Traditionally, Ehrlich's tumor is used in experimental oncology to investigate the therapeutic capacity of different synthetic chemotherapeutic agents or to evaluate the antitumoral activity of different substances of natural origin. However, the understanding of immune mechanisms during Ehrlich carcinogenesis is still limited. In this review, we seek to describe the immune response during Ehrlich's tumor growth, and natural response without the influence of pharmacological administration, immunotherapies or concomitant challenges. The study followed the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). A systematic review was carried out that included experimental trials with mice challenged with Ehrlich's tumor. The research was carried out in three databases including MEDLINE/PubMed, Scopus, Latin American and Caribbean Literature in Health Sciences (LILACS). The searches resulted in 913 papers being found, of which 55 articles were considered eligible, and of these 55, 29 were selected for analysis. Findings indicate that there is an increase in the expression of M2 and T Helper (TH2) macrophages and of the cytokines IL-17, IL-1B, IL-6 and PGE in the ascitic form of Ehrlich. These phenotypic expressions are also found in ascitic neoplasms in humans. Ehrlich's solid tumor was characterized by increased expression of CD4, CD8, neutrophils and TNF-a, Foxp3 + and Qa-2 +, and these characteristics are analogous to human breasts cancers. It is our understanding that further studies are needed to assess the immune mechanisms in Ehrlich's tumor, since these findings can be used to improve cancer treatments that are analogous to Ehrlich's tumor.