Immunological and inflammatory responses in the kidneys in experimental acanthamoebiasis

TL;DR

This study explores how the immune system responds in the kidneys during Acanthamoeba infection in mice, revealing changes in inflammation-related proteins and cytokines.

Contribution

The study identifies specific immune response patterns in the kidneys of infected mice, offering new insights into acanthamoebiasis pathophysiology.

Findings

Early infection in immunocompetent mice showed elevated IFNγ, TNFα, PTGS2/COX-2, and IL-17A mRNA levels.

Late-stage infection in immunocompetent mice showed decreased levels of NLRP3, IL-1β, IL-10, and several cytokines.

Immunosuppressed mice showed higher NLRP3, PTGS2/COX-2, and cytokine expressions but lower IL-18 in infected kidneys.

Abstract

The pathomechanisms of Acanthamoeba spp. infection are still poorly understood. The aim of the study was to determine the expression of the NLR family pyrin domain-containing protein 3 (NLRP3), prostaglandin-endoperoxide synthase 2 (PTGS2, commonly known as cyclooxygenase-2, COX-2), and various cytokines in the kidneys of immunocompetent and immunosuppressed mice infected with Acanthamoeba sp. (T16 genotype). The proteins were analyzed by quantitative reverse transcription PCR. In immunocompetent mice, we observed increased mRNA levels of interferon gamma (IFNγ), tumor necrosis factor alpha (TNFα), PTGS2/COX-2, and interleukin (IL)-17A at the beginning of infection. While in the late stages, we found decreased levels of NLRP3, IL-1β, IL-10, IL-17A, IL-21, IL-23, IFNγ, TNFα, and macrophage inflammatory protein-2 (MIP-2) in the kidneys of infected hosts compared to uninfected ones. In immunosuppressed mice, we noted higher expressions of NLRP3, PTGS2/COX-2, IL-1β, IL-10, IL-17A, IL-21, IFNγ, TNFα, and MIP-2, and lower expression of IL-18 in the infected mice compared to the control group. The basic understanding of the immune response during Acanthamoeba sp. infection is critical to improving clinical outcomes and also has significant implications for developing therapeutic interventions. Here, we have reported the inflammatory responses in the kidneys infected with Acanthamoeba sp. However, additional studies are needed to understand the specific beneficial and detrimental roles of the cytokine response.

Acanthamoeba spp. are significant biological factors and can cause rare infections characterized by high mortality and difficulty with treatment. One of the reasons Acanthamoeba spp. persist so effectively in the body is a lack of knowledge about the pathomechanisms and pathophysiology of infections. Recent studies showed that Acanthamoeba spp. can also infect the kidneys in the hosts, being an important cause of medical complications. A better understanding of the mechanisms by which Acanthamoeba spp. cause kidney injury could lead to more effective treatments for systemic acanthamoebiasis.

Figures