Potential Biomarkers in Diagnosis of Renal Acanthamoebiasis

Kot, Karolina; Kupnicka, Patrycja; Witulska, Oliwia; Czepan, Aleksandra; Łanocha-Arendarczyk, Natalia; Łanocha, Aleksandra; Kosik-Bogacka, Danuta

doi:10.3390/ijms22126583

Cited by 5 publications

(9 citation statements)

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“…have been found to increase the expression of Toll-like receptor 2 (TLR2) in the host kidney; TLRs are significant components of the innate immune response that are responsible for recognizing pathogen-associated molecular patterns (PAMPs) [ 28 ]. Additionally, increased expression and activity of matrix metalloproteinases -2 and -9 (MMP-2 and MMP-9) were observed in the kidneys of hosts with systemic acanthamoebiasis [ 10 ]. MMPs are considered to be some of the most important proteins degrading the components of the extracellular matrix (ECM), which affects physiological and pathological processes.…”

Section: Discussionmentioning

confidence: 99%

“…Most of the parasites cause changes in the kidneys, which are usually unnoticed because they are masked by extrarenal manifestations. The exact mechanisms of kidney injury caused in parasitic infections are poorly known in many cases, resulting in major difficulties to provide specific therapeutic interventions [ 10 ]. Therefore, research on the pathophysiology of kidney infection by parasites is very significant.…”

Section: Discussionmentioning

confidence: 99%

“…Increased ROS levels activate antioxidant defense mechanisms and Nrf2 gene expression and/or protein concentration. NADPH oxidases probably activate MMP9 [ 10 ]. In the histopathological examination of the kidneys of immunocompetent infected mice, lymphocyte infiltration and mitotic figures were found [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

“…The animal model has been described previously [ 10 , 23 ]. Briefly, 96 male BALB/c mice, 6–10 weeks of age, were used in the study.…”

Section: Methodsmentioning

confidence: 99%

“…Many clinical cases described in the scientific literature do not report whether the kidneys were studied for the presence of amoebae during post-mortem examinations [ 6 – 9 ]. Animal studies, on the other hand, have clearly revealed that amoebae are transported in the blood system and penetrate the kidneys where they can cause dysfunction [ 10 ]. Understanding the pathomechanisms of infection through biochemical and molecular studies of the Acanthamoeba spp.-host system is essential for the development of new diagnostic procedures and the identification of new therapeutic targets that will limit the degree of cell and organ damage.…”

Section: Introductionmentioning

confidence: 99%

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The role of apoptosis and oxidative stress in the pathophysiology of Acanthamoeba spp. infection in the kidneys of hosts with different immunological status

Kot,

Kupnicka,

Tarnowski

et al. 2023

Parasites Vectors

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Background Acanthamoeba spp. are opportunistic pathogens that cause inflammation, mostly in the brain, lungs and cornea. Recent reports indicate kidney dysfunction in hosts with systemic acanthamoebiasis. The aim of the study was to analyze the gene expression and protein concentration of NADPH oxidase 2 and 4 (NOX2 and NOX4, respectively) and nuclear erythroid 2-related factor (Nrf2) in the kidneys of hosts with systemic acanthamoebiasis. We also aimed to determine the protein and gene expressions of Bcl2, Bax, caspases 3 and 9. Methods Mice were divided into four groups based on their immunological status and Acanthamoeba sp. infection: A, immunocompetent Acanthamoeba sp.-infected mice; AS, immunosuppressed Acanthamoeba sp.- infected mice; C, immunocompetent uninfected mice; CS, immunosuppressed uninfected mice. NOX2, NOX4 and Nrf2 were analyzed by quantitative reverse transcription PCR (qRT-PCR) and ELISA methods, while pro-apoptotic and anti-apoptotic proteins (Bax and Bcl-2, respectively), Cas9, Cas3 were analyzed by qRT-PCR and western blot methods. Results Increased gene expression and/or protein concentration of NOX2 and NOX4 were found in both immunocompetent and immunosuppressed mice infected with Acanthamoeba sp. (groups A and AS, respectively). Gene expression and/or protein concentration of Nrf2 were higher in group A than in control animals. Compared to control mice, in the AS group the expression of the Nrf2 gene was upregulated while the concentration of Nrf2 protein was decreased. Additionally in A group, higher gene and protein expression of Bcl-2, and lower gene as well as protein expression of Bax, caspases 3 and 9 were noted. In contrast, the AS group showed lower gene and protein expression of Bcl-2, and higher gene as well as protein expression of Bax, caspases 3 and 9. Conclusions This study is the first to address the mechanisms occurring in the kidneys of hosts infected with Acanthamoeba sp. The contact of Acanthamoeba sp. with the host cell surface and/or the oxidative burst caused by elevated levels of NOXs lead to an antioxidant response enhanced by the Nrf2 pathway. Acanthamoeba sp. have various strategies concerning apoptosis. In immunocompetent hosts, amoebae inhibit the apoptosis of kidney cells, and in immunosuppressed hosts, they lead to increased apoptosis by the intrinsic pathway and thus to a more severe course of the disease. Graphical Abstract

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…The animal model has been described previously [ 10 , 23 ]. Briefly, 96 male BALB/c mice, 6–10 weeks of age, were used in the study.…”

Section: Methodsmentioning

confidence: 99%