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Acute kidney injury (AKI) is an important health problem, affecting 13.3 million individuals/year. It is associated with increased mortality, mainly in low- and middle-income countries, where renal replacement therapy is limited. Moreover, survivors show adverse long-term outcomes, including increased risk of developing recurrent AKI bouts, cardiovascular events, and chronic kidney disease. However, there are no specific treatments to decrease the adverse consequences of AKI. Epidemiological and preclinical studies show the pathological role of inflammation in AKI, not only at the acute phase but also in the progression to chronic kidney disease. Toll-like receptors (TLRs) are key regulators of the inflammatory response and have been associated to many cellular processes activated during AKI. For that reason, a number of anti-inflammatory agents targeting TLRs have been analyzed in preclinical studies to decrease renal damage during AKI. In this review, we updated recent knowledge about the role of TLRs, mainly TLR4, in the initiation and development of AKI as well as novel compounds targeting these molecules to diminish kidney injury associated to this pathological condition, The authors work has been supported by grants from Instituto de Salud Carlos III (ISCIII, FIS-FEDER PI17/00130, PI17/01495, PI20/00375, PI20/00487), Spanish Biomedical Research Centre in Diabetes and Associated Metabolic Disorders (CIBERDEM) and Cardiovascular (CIBERCV), Spanish Ministry of Science and Innovation (RTI2018-099114-B-100, RTI2018-098788-B-100, DTS19/00093, RYC-2017-22369), and Spanish Societies of Cardiology (SEC), Nephrology (SEN) and Atherosclerosis (SEA). The “PFIS” and “Sara Borrell” training program of the ISCIII supported the salary of MGH (FI18/00310), SR-M (CD19/00021) and CH-B (CP16/00017). Córdoba University supported the salary of C.G.C.

Simple Summary Little information is currently available on the epidemiology of parasitic and commensal protist species in captive non-human primates (NHP) and their zoonotic potential. This study investigates the occurrence, molecular diversity, and potential transmission dynamics of parasitic and commensal protist species in a zoological garden in southern Spain. The prevalence and genotypes of the main enteric protist species were investigated in faecal samples from NHP, zookeepers and free-living rats by molecular (PCR and sequencing) methods. A high prevalence of the diarrhoea-causing protists Giardia duodenalis and Blastocystis sp. (but not Cryptosporidium spp.) was observed in captive NHP at the Córdoba Zoo Conservation Centre. NHP can harbour zoonotic genotypes of G. duodenalis, Blastocystis sp., and Enterocytozoon bieneusi. Indeed, strong evidence of the occurrence of Blastocystis zoonotic transmission between NHP and their handlers was provided, despite the use of personal protective equipment and the implementation of strict health and safety protocols. Free-living sympatric rats are infected by host-specific species/genotypes of the investigated protists and seem to play a limited role as source of infections to NHP or humans in this setting. The extent of these findings should be confirmed in similar epidemiological surveys targeting other captive NHP populations. Abstract Little information is currently available on the epidemiology of parasitic and commensal protist species in captive non-human primates (NHP) and their zoonotic potential. This study investigates the occurrence, molecular diversity, and potential transmission dynamics of parasitic and commensal protist species in a zoological garden in southern Spain. The prevalence and genotypes of the main enteric protist species were investigated in faecal samples from NHP (n = 51), zookeepers (n = 19) and free-living rats (n = 64) by molecular (PCR and sequencing) methods between 2018 and 2019. The presence of Leishmania spp. was also investigated in tissues from sympatric rats using PCR. Blastocystis sp. (45.1%), Entamoeba dispar (27.5%), Giardia duodenalis (21.6%), Balantioides coli (3.9%), and Enterocytozoon bieneusi (2.0%) (but not Troglodytella spp.) were detected in NHP. Giardia duodenalis (10.5%) and Blastocystis sp. (10.5%) were identified in zookeepers, while Cryptosporidium spp. (45.3%), G. duodenalis (14.1%), and Blastocystis sp. (6.25%) (but not Leishmania spp.) were detected in rats. Blastocystis ST1, ST3, and ST8 and G. duodenalis sub-assemblage AII were identified in NHP, and Blastocystis ST1 in zookeepers. Giardia duodenalis isolates failed to be genotyped in human samples. In rats, four Cryptosporidium (C. muris, C. ratti, and rat genotypes IV and V), one G. duodenalis (assemblage G), and three Blastocystis (ST4) genetic variants were detected. Our results indicate high exposure of NHP to zoonotic protist species. Zoonotic transmission of Blastocysts ST1 was highly suspected between captive NHP and zookeepers.