RESUMO
Recently, a number of studies have reported the presence of interleukin 17 (IL-17) in patients with Lyme disease, and several murine studies have suggested a role for this cytokine in the development of Lyme arthritis. However, the role of IL-17 has not been studied using the experimental Lyme borreliosis model of infection of C3H mice with Borrelia burgdorferi. In the current study, we investigated the role of IL-17 in the development of experimental Lyme borreliosis by infecting C3H mice devoid of the common IL-17 receptor A subunit (IL-17RA) and thus deficient in most IL-17 signaling. Infection of both C3H and C3H IL-17RA(-/-) mice led to the production of high levels of IL-17 in the serum, low levels in the heart tissue, and no detectable IL-17 in the joint tissue. The development and severity of arthritis and carditis in the C3H IL-17RA(-/-) mice were similar to what was seen in wild-type C3H mice. In addition, development of antiborrelia antibodies and clearance of spirochetes from tissues were similar for the two mouse strains. These results demonstrate a limited role for IL-17 signaling through IL-17RA in the development of disease following infection of C3H mice with B. burgdorferi.
Assuntos
Artrite/imunologia , Artrite/patologia , Doença de Lyme/imunologia , Doença de Lyme/patologia , Miocardite/imunologia , Miocardite/patologia , Receptores de Interleucina-17/deficiência , Animais , Borrelia burgdorferi/crescimento & desenvolvimento , Feminino , Interleucina-17/sangue , Camundongos Endogâmicos C3H , Camundongos Knockout , Índice de Gravidade de DoençaRESUMO
Seminal plasma uterine priming is important for pregnancy and offspring phenotype in mice and swine; however, impacts on the uterus of the dam and her offspring in cattle are unknown. We sought to determine the effects of seminal plasma uterine priming at estrus on uterine transcriptomics, early gestation (d 35, 40, and 45) embryo morphometrics, mid- to late-gestation (d 140 to 220) uterine artery hemodynamics, birth morphometrics, and liver transcriptomics in offspring at 30 d of age. Multiparous Angus-based commercial beef cows were randomly assigned to receive treatment at estrus: 0.5 mL pooled seminal plasma in the uterine body (n = 31, seminal plasma primed) or no treatment (n = 31, control). Seven d later a subset of cows (n = 4/treatment) underwent uterine biopsies, and the remaining cows underwent embryo transfer. Embryo crown-rump length and uterine artery hemodynamics were measured during gestation using ultrasonography. Morphometrics of the calf were collected within 24 h of parturition. Liver biopsies were collected at 30 d of age. Data were analyzed by ANOVA in a completely randomized design for the effect of treatment. Myosin heavy chain I (JSP.1) was downregulated [Benjamin-Hochberg adj P (BH) <= 0.05] and ABO alpha 1-3-N-acetylgalactosaminyltransferase and alpha 1-3-galactosyltransferase (ABO) was upregulated (BH adj P <= 0.05) in the uterus of seminal plasma primed cows 7 d after treatment. Embryo crown-rump length was less (P < 0.05) in seminal plasma primed cows. Mid- to late-gestation (d 140 to 220) uterine artery resistance was increased (P < 0.05) in seminal plasma primed cows. Seminal plasma priming did not alter birth weights or curve-crown-rump length, but heart girth was increased (P < 0.05) in offspring from seminal plasma primed cows. There were no differentially expressed genes (BH adj P <= 0.05) in offspring liver at 30 d of age; however, myosin light chain, phosphorylatable, fast skeletal muscle (MYLPF) was absent in all liver samples from calves from seminal plasma primed cows. In contrast, vomeronasal 1 receptor bosTauV1R414 (BOSTAUV1R414) was present in 6 of the 7 liver samples from calves from seminal plasma primed cows. Seminal plasma uterine priming alters uterine transcriptomics, negatively impacts early gestation embryo growth and mid- to late-gestation uterine artery resistance suggesting downstream vascular anomalies. However, these in utero conditions did not impact offspring from birth to 30 d of age.
RESUMO
The objectives were to examine melatonin-mediated changes in temporal uterine blood flow (UBF), vaginal temperatures (VTs), and fetal morphometrics in 54 commercial Brangus heifers (Fall, n = 29; Summer, n = 25) during compromised pregnancy. At day 160 of gestation, heifers were assigned to one of the four treatments consisting of adequately fed (ADQ-CON; 100% National Research Council [NRC]; n = 13), global nutrient restricted (RES-CON; 60% NRC; n =13), and ADQ or RES supplemented with 20 mg/d of melatonin (ADQ-MEL, n = 13; RES-MEL, n = 15). In the morning (0500 hours; AM) and afternoon (1300 hours; PM) of day 220 of gestation, UBF was determined via Doppler ultrasonography, while temperature data loggers attached to progesterone-free controlled internal drug releases were used to record VTs. At day 240 of gestation, heifers underwent cesarean sections for fetal removal and morphometrics determination. The UBF and VT data were analyzed using repeated measures of analysis of variance (ANOVA), while the morphometrics was analyzed using the MIXED procedure of SAS. Seasons were analyzed separately. In Fall, a nutrition by treatment interaction was observed, where the RES-CON heifers exhibited reduced total UBF compared with ADQ-CON (5.67 ± 0.68 vs. 7.97 ± 0.54 L/min; P = 0.039). In Summer, MEL heifers exhibited increased total UBF compared with the CON counterparts (8.16 ± 0.73 vs. 6.00 ± 0.70 L/min; P = 0.048). Moreover, there was a nutrition by treatment by time interaction in VT for Fall and Summer heifers (P ≤ 0.005). In Fall, all groups had decreased VT in the morning compared with the afternoon (P < 0.05). Whereas, in Summer, VT increased for ADQ-CON and RES-CON (P < 0.0001) from morning to afternoon, the ADQ-MEL and RES-MEL remained constant throughout the day (P = 0.648). Furthermore, the RES-MEL-PM exhibited decreased VT compared with ADQ-CON-PM (38.91 ± 0.09 vs. 39.26 ± 0.09 °C; P = 0.018). Lastly, in Fall, a main effect of nutrition was observed on fetal weights, where the RES dams had fetuses with decreased body weight when compared with ADQ (24.08 ± 0.62 vs. 26.57 ± 0.64 kg; P = 0.0087). In Summer, a nutrition by treatment interaction was observed on fetal weights where the RES-CON dams had fetuses with reduced weight when compared with ADQ-CON and RES-MEL (P < 0.05). In summary, nutrient restriction decreased UBF and melatonin supplementation increased UBF depending on the season. Additionally, melatonin appeared to decrease VT and rescue fetal weights when supplemented in the Summer.