RESUMEN
Signaling driven by nucleic acid sensors participates in interferonopathy-mediated autoimmune diseases. NLRP12, a pyrin-containing NLR protein, is a negative regulator of innate immune activation and type I interferon (IFN-I) production. Peripheral blood mononuclear cells (PBMCs) derived from systemic lupus erythematosus (SLE) patients expressed lower levels of NLRP12, with an inverse correlation with IFNA expression and high disease activity. NLRP12 expression was transcriptionally suppressed by runt-related transcription factor 1-dependent (RUNX1-dependent) epigenetic regulation under IFN-I treatment, which enhanced a negative feedback loop between low NLRP12 expression and IFN-I production. Reduced NLRP12 protein levels in SLE monocytes was linked to spontaneous activation of innate immune signaling and hyperresponsiveness to nucleic acid stimulations. Pristane-treated Nlrp12-/- mice exhibited augmented inflammation and immune responses; and substantial lymphoid hypertrophy was characterized in NLRP12-deficient lupus-prone mice. NLRP12 deficiency mediated the increase of autoantibody production, intensive glomerular IgG deposition, monocyte recruitment, and the deterioration of kidney function. These were bound in an IFN-I signature-dependent manner in the mouse models. Collectively, we reveal a remarkable link between low NLRP12 expression and lupus progression, which suggests the impact of NLRP12 on homeostasis and immune resilience.
Asunto(s)
Lupus Eritematoso Sistémico , Nefritis Lúpica , Ácidos Nucleicos , Animales , Ratones , Epigénesis Genética , Inmunidad Innata , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Leucocitos Mononucleares , Lupus Eritematoso Sistémico/genética , Interferones/metabolismoRESUMEN
Urogenital schistosomiasis is a chronic parasitic disease that causes severe morbidity among schoolchildren in many poor-resource communities in Nigeria. We investigated the prevalence, intensity, and risk factors of the infection in three communities of Kwara State to ascertain the current status of the disease. Of the 724 urine samples screened, using filtration method, 332 (45.6%) school-aged children were infected with average intensity and mean population eggs load of 127.9 eggs/10 ml of urine and 0.794, respectively. Prevalence and intensity of infection varied with communities: high in Ajase-Ipo (57.1%; X = 100.7 ± 23.01 eggs/10 ml) and low in Shonga (37.5%; X = 91.4 ± 78.0). Infection was significantly (P < 0.05) higher in males (50.8%) than the females (42.4%). Similarly, infection significantly (P < 0.05) increased with increasing age. Multivariate logistic analysis of risk factors revealed that lack of portable drinking water (adjusted odd ratio (aOR) = 4.76; 95% CI = 2.64-5.98), unemployment (aOR = 2.23; 1.87-2.294), lack of knowledge of infection (aOR = 2.16; 0.59-3.83), and frequent contact with contaminated water bodies (aOR = 2.01; 1.45-2.70) were important predictors of urinary schistosomiasis. Therefore, continuous evaluation of the intervention strategies that address risk factors must compliment Mass Drug Administration to curtail the transmission and debilitating health consequences of infection in endemic settings.