Editorial: The innate and adaptive immune system in human urinary system

The urinary, the immune and the nervous systems communicate with each other to create an effective network in healthy human body. The kidneys and the bladder are known as the main parts of the urinary system which are joint together via ureters. (1)(2)(3). The urinary system maintains homeostasis through the innate and adaptive immune cells (like macrophages (MΦs)). These immune cells express a wide range of immune biomolecules including interleukins (ILs) and pattern-recognition receptors (PRRs) e.g., toll-like receptors (TLRs). Due to this knowledge, microglia as specialized MΦs of the central nervous system (CNS) are effective phagocytotic cells that produce different types of PRRs such as TLRs. The functions of microglia are regulated by pro-inflammatory and anti-inflammatory cytokines receptors (4-6). Hence, both of the immune and the nervous systems have pivotal role in maintenance of homeostasis in the human urinary system.Because of the importance of this topic, the editors decided to run the present impactful Research Topic in the prestigious journal of Frontiers in Immunology. Our purpose was to collect a treasure trove of strong and useful research studies. Fortunately, we succeeded in our attempt to collect six thematic publications from 54 international authors.In a cross-sectional study, Qin et al. investigated the systematic immune-inflammation index (SII) as a novel inflammatory marker and its association with albuminuria. In this regard, they obtained the related data including the SII and urinary albumin-to-creatinine ration (ACR) pertaining to 36,463 adults (females=50.96% males=49.04%) during 13 years between 2005 and 2018 from National Health and Nutrition Examination Survey (NHANES). A wide range of covariates e.g., race, gender, body mass index (BMI), age, diabetes, behavioral condition comprising smoking, etc. were included in this study. Their findings show a positive relationship between SII and enhancement of urinary albumin excretion among US adults in this survey.In another investigation, Wang et al. have studied the correlation between the profile of urinary complements in patients with IgA nephropathy (IgAN) and the associated clinical and pathological characteristics. This survey was performed in a period of three years (2019-2022) regarding 213 urine samples taken from 213 individuals (68 individuals were healthy controls, while the left persons were patients with IgAN (n=95) and membranous nephropathy (MN) (n=68)) at Sichuan Provincial People's hospital, China. Wang et al. focused on urinary complement proteins. This team demonstrated the presence of 44 complement proteins in patients with IgAN. They also showed that the unusual increase of complement proteins in patients with IgAN was in association with renal histological damages, decreased renal functions and proteinuria. Hence, Wang et al. suggested that the urinary complement profile could be recognized as a potential biomarker panel to monitor and treat the patients with IgAN.Jin-Hee Park et al. demonstrated the inhibitory effects of lomerizine on lipopolysaccharide (LPS)mediated neuroinflammation and tau hyperphosphorylation through modulating NLRP3, DYRK1A and GSK3α/ßLPS in both in vitro and in vivo conditions. Lomerizine acts as L-and Ttype voltage-gated calcium channels antagonist. Microglia as a part of innate immune cells are activated in CNS through the microbial components e.g., LPS, or other stimuli including neural damages, injuries, etc. Their findings showed that, lomerizine can be recognized as a potential therapeutic alternative in patients with neuroinflammation-or taupathy-related diseases.Eggers et al. present the effect of a German-licensed vaccine, Stro Vac® (Strathmann, Hamburg) which is used against recurrent urinary tract infectionss (rUTIs). This vaccine is composed of an adjuvant (aluminum phosphate) and ten heat-inactivated bacterial pathogens including six different strains of Escherichia coli and one strain of four different species such as Enterococcus faecalis, Klebsiella pneumoniae, Morganella morganii, and Proteus mirabilis. They showed that, this vaccine is able to activate both of the innate and adaptive immune system against the etiological agents of rUTIs.Jung-Woo Seo et al. investigated the potential role of urinary exosomal microRNA biomarkers as an innovative molecular diagnostic approach for acute rejection (AR) in kidney transplant recipients (KTRs). This method was validated through determination of the urinary exosomal microRNA signatures as novel and non-invasive biomarkers. In this regard, they studied the urinary exosomal microRNA profiles pertaining to KTRs. The development and validation of the urinary exosomal microRNA profiles in KTRs was achieved by studying the published literatures, recruitment of NanoString-based transcriptomics and public data bases, etc. This team showed that, the urinary exosomal microRNA signatures could be recognized as suitable potential biomarkers to detect AR in KTRs; however, further investigations are needed.And the next paper published by Mazzarino et al. suggests two therapeutic methods regarding the reduction of chronic vascular inflammation (CVI) and lower cardiovascular (CV) pathology in patients with chronic kidney disease (CKD)-associated DAMPs. In this regard, the blood samples were taken from patients with CKD (stage 5). This team presented two therapeutic strategies to decrease CVI and lower CV pathology in CKD. Due to this fact, Mazzarino et al. used paquinimod to prevent calprotectin-TLR4/CD14 interaction in single DAMP-targeting strategy, while they recruited soluble TLR2 (sTLR2) to prevent TLR2-DAMP interaction and CD14-dependent TLRs activation, and inhibition of CD14 co-receptor activities in their second strategy named as multi-TLR blocking strategy. Simultaneously, the sTLR2 supported the suboptimal CD14-independent TLR activation. All in all, the former strategy decreased the CKD-associated vascular inflammation via inhibiting a single DAMP's activity, while the latter strategy reduced the multiple DAMPs' activities to decrease the CKD-associated vascular inflammation.Replacement of the current antibiotic therapy by the effective preventive procedures like consumption of vaccines, agonists and antagonists may minimize the global concern regarding the classic pharmaceutical therapies and the related threats including the rise of antimicrobial resistance (AMR) feature, worldwide. Hence, this occurrence may be a promising alternative (7)(8)(9)(10). Indeed, "prevention is better than cure".