Probiotic Lactobacillus kefiri prevents endotoxin-induced preterm birth and stillbirth in mice.

Preterm birth (PTB), defined as birth occurring before 37 weeks of pregnancy, affects 5-18% of pregnancies and is the leading cause of neonatal morbidity and mortality worldwide. Although PTB is considered a syndrome, infection-induced inflammation accounts for up to 50% of all cases. Despite the effort to reduce the incidence of PTB, it continues to rise worldwide and current approaches for preventing or treating PTB are largely unsatisfactory. Probiotics are live microorganisms which, when administered in adequate amounts, confer a health benefit on the host. It is well known that probiotics can modulate the host immune system exerting a potent anti-inflammatory activity. The main aim of this work was to evaluate the capacity of the probiotic Lactobacillus kefiri (Lk48) to prevent preterm birth in mice. C57BL/6 female mice were treated with Lk48 or vehicle a week before and during pregnancy and were challenged with LPS (10 µg), a dose known to induce PTB on gestational day 16. Percentages of PTB as well as stillbirth were evaluated. We observed that oral administration of Lk48 significantly reduced the occurrence of LPS-induced PTB and stillbirth as well as improved post-natal development. This protective effect was associated with a reduction in leucocyte infiltration and reduced inflammation-induced damage in reproductive tissue. Besides, Lk48 treatment also modulated the diversity of vaginal microbiota. Our results demonstrated that prophylactic consumption of probiotic L. kefiri prevented LPS-induced PTB and still birth in mice and opens new avenues for exploring novel and promising strategies for preventing PTB in humans.

Sífilis maligna en paciente con infección por el virus de la inmunodeficiencia humana / Malignant syphilis in a patient with HIV infection

Resumen La sífilis maligna asociada al virus de la inmunodeficiencia humana (HIV). Se presenta con lesiones nodulares cutáneas con tendencia a la ulceración. Entre sus hallazgos histopatológicos se destaca la presencia de granulomas no caseificantes, lo cual obliga al diagnóstico diferencial con otras patologías granulomatosas infecciosas y no infecciosas. La evolución de la enfermedad es favorable con el tratamiento con penicilina en la mayoría de los casos. Presentamos el caso de una paciente con infección por HIV que cumple criterios diagnósticos de sífilis maligna y alertamos sobre esta entidad granulomatosa poco frecuente.

Abstract Malignant syphilis occurs frequently in patients infected with human immunodeficiency virus (HIV) and presents with cutaneous nodular lesions that tend to ulcerate. Non caseating granulomas are among the most conspicuous histopathological findings and require differential diagnosis with other infectious and non-infectious granulomatous conditions. The evolution of the disease is usually favourable with penicillin treatment. We present the case of an HIV-positive patient who meets diagnostic criteria for malignant syphilis and alert on this infrequent granulomatous entity.

[Malignant syphilis in a patient with HIV infection]. / Sífilis maligna en paciente con infección por el virus de la inmunodeficiencia humana.

Malignant syphilis occurs frequently in patients infected with human immunodeficiency virus (HIV) and presents with cutaneous nodular lesions that tend to ulcerate. Non caseating granulomas are among the most conspicuous histopathological findings and require differential diagnosis with other infectious and non-infectious granulomatous conditions. The evolution of the disease is usually favourable with penicillin treatment. We present the case of an HIV-positive patient who meets diagnostic criteria for malignant syphilis and alert on this infrequent granulomatous entity.

La sífilis maligna asociada al virus de la inmunodeficiencia humana (HIV). Se presenta con lesiones nodulares cutáneas con tendencia a la ulceración. Entre sus hallazgos histopatológicos se destaca la presencia de granulomas no caseificantes, lo cual obliga al diagnóstico diferencial con otras patologías granulomatosas infecciosas y no infecciosas. La evolución de la enfermedad es favorable con el tratamiento con penicilina en la mayoría de los casos. Presentamos el caso de una paciente con infección por HIV que cumple criterios diagnósticos de sífilis maligna y alertamos sobre esta entidad granulomatosa poco frecuente.

Expression of IL-33 Receptor Is Significantly Up-Regulated in B Cells During Pregnancy and in the Acute Phase of Preterm Birth in Mice.

Interleukin-33 (IL-33) is a mucosal alarmin belonging to the IL-1 cytokine family and is now recognized to have a key role in innate and adaptive immunity, contributing to tissue homeostasis and response to environmental stresses. In addition, IL-33 has also been shown to work as a positive regulator that initiates and maintains a Th2 immune response. In the context of pregnancy, it has been recently demonstrated that upon certain stress conditions, such as an infection induced inflammation, IL-33 is released from the uterine mucosa and triggers decidual B cells to produce anti-inflammatory molecules, which in turn restore immune homeostasis and prevents the development of preterm birth. In this study we therefore performed a detailed characterization of IL-33 receptor (Il1rl1 or ST2) expression in B cells during normal pregnancy, as well as in a mouse model of preterm birth. We observed that splenic B cells significantly up-regulate the expression of Il1rl1 during pregnancy and identified the B1 B cell population as the main ST2-expressing B cell subset. A further kinetic analysis showed that percentages of ST2-expressing B1 B cells are significantly augmented on days 12 and 14 of pregnancy, both in the spleen and peritoneal cavity of pregnant mice, and then drop toward the end of pregnancy to the levels observed in non-pregnant animals. Furthermore, using a mouse model of LPS-induced preterm birth, we demonstrated that not only are the percentages of ST2-expressing B1 B cells significantly enlarged in the spleen during the acute phase of preterm birth, but decidual B cells also significantly up-regulate ST2 expression as compared to term-pregnant mice. Overall, our results suggest a functional role of ST2 expression in B cells during pregnancy and reinforce the importance of the IL-33/ST2 axis in B cells as a critical mechanism to control inflammation-induced preterm birth.