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Immune activity during pregnancy must be tightly regulated to ensure successful pregnancy. This regulation includes the suppression of inflammatory activity that could target the semi-allogeneic fetus. Tregs are immunosuppressive; Th17 cells are pro-inflammatory. A precise balance in the two cell populations is critical to pregnancy maintenance, wh...
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... In the domestic female cat, as in other mammals, this system acts from the uterine and ovarian morphological changes that occur during the estrous cycle and during pregnancy [14,26]. Therefore, any dysregulation in the expression of these mediators is closely related to important pathological conditions in domestic cats, such as uterine hyperplasias and pyometra [14], in addition to infections caused by FIV [33,34,153]. ...
... In the full-term placenta, however, a reduction was observed in IL-4, IL-12P35, IL-12p40, and IL-1B [33,34] and an increase in Il-6 [33]. In addition to these changes, Chumbley et al. [153] demonstrated that the placental gene expression of FOXP3 and RORΓ was reduced in early pregnancy in FIV-infected cats, suggesting an imbalance in T-lymphocyte and T-lymphocyte helper 17 (Th17) populations at this gestational stage. ...
... Similarly, Scott et al. [33] described the reduction of several cytokines in early pregnancy (IL-4, IL-5, IL-6, IL-1β, IL-12P35, IL-12P40, and CXCR4) or late pregnancy (IL4, IL-12P35, and IL-12P40). Chumbley et al. [153] also demonstrated the reduced placental expression of IL-10, IL-2, IL-17a, IL-6, and TGF-β in FIV-positive cats with non-viable fetuses in early pregnancy. ...
Simple Summary
This article presents the current knowledge regarding the modulation and expression profile of hormonal, immunological, redox, and growth mediators involved in the reproductive morphophysiology of the domestic cat.
Abstract
The domestic cat (Felis catus) is considered an important model for the study of feline reproductive morphophysiology. However, although the morphological changes and clinical signs that occur during the estrous cycle and pregnancy are well known, little is known about the molecular mechanisms involved in the reproductive physiology of this animal species. Thus, this paper reviews the current knowledge about the modulation and expression profile of hormonal, immunological, redox, and growth mediators involved in the uterine, ovarian, and placental morphophysiology of domestic cats.
... There was also an increase in CD4 + CCR6 + lymphocytes in the mandibular lymph nodes of cART-treated FIV+ cats. CCR6 are a marker of the Th17 lymphocyte subtype [61,75,76], which are also proinflammatory cells [77] that can support FIV replication [78,79]. Th17 cells and IL-17 receptor signaling are essential for mucosal host defense against pathogens, and a decrease in Th17 cells due to HIV and FIV infection has been attributed to the development of lentiviral-induced oral disease [12,38,80]. ...
Feline Immunodeficiency Virus (FIV) causes progressive immune dysfunction in cats similar to human immunodeficiency virus (HIV) in humans. Although combination antiretroviral therapy (cART) is effective against HIV, there is no definitive therapy to improve clinical outcomes in cats with FIV. This study therefore evaluated pharmacokinetics and clinical outcomes of cART (2.5 mg/kg Dolutegravir; 20 mg/kg Tenofovir; 40 mg/kg Emtricitabine) in FIV-infected domestic cats. Specific pathogen free cats were experimentally infected with FIV and administered either cART or placebo treatments (n = 6 each) for 18 weeks, while n = 6 naïve uninfected cats served as controls. Blood, saliva, and fine needle aspirates from mandibular lymph nodes were collected to quantify viral and proviral loads via digital droplet PCR and to assess lymphocyte immunophenotypes by flow cytometry. cART improved blood dyscrasias in FIV-infected cats, which normalized by week 16, while placebo cats remained neutropenic, although no significant difference in viremia was observed in the blood or saliva. cART-treated cats exhibited a Th2 immunophenotype with increasing proportions of CD4+CCR4+ cells compared to placebo cats, and cART restored Th17 cells compared to placebo-treated cats. Of the cART drugs, dolutegravir was the most stable and long-lasting. These findings provide a critical insight into novel cART formulations in FIV-infected cats and highlight their role as a potential animal model to evaluate the impact of cART on lentiviral infection and immune dysregulation.
... Surprisingly, when wild type and the variant lacking in exon 2 were expressed in a cell, the suppressive activity was enhanced, as compared a single version expressing cells suggesting a critical role of exon 2 in activity of Treg (111). Cytokines shown to promote Th17 responses in cats are IL-1β, IL-6, TGF-β, and IL-21 (113). Foxp3 + Treg have been demonstrated in animals that include pigs, cows, sheep, goat, horses, baboon, macaque, chimpanzee, harbor seals, and walrus (109). ...
... For example, similarities in the pathogenesis of feline immunodeficiency virus (FIV) and HIV make the cat a useful animal model (184). FIV was shown to infect Treg and this made them better suppressors (113,185). FIV infected cats exhibit an early depletion of CD4 + T cells and enhanced Treg activity, which in turn compromises anti-viral adaptive immunity. This provides the virus an opportunity to establish a productive infection (186). ...
... This provides the virus an opportunity to establish a productive infection (186). More recent reports suggest a dysregulation of Treg and Th17 cells during FIV pathogenesis in cats during a systemic infection as well as in the placenta leading to non-viable pregnancies (113). Whether or not a similar situation exists in pregnant women infected with HIV is not known. ...
It is now clear that the outcome of an inflammatory process caused by infections depends on the balance of responses by several components of the immune system. Of particular relevance is the interplay between regulatory T cells (Tregs) and CD4⁺ T cells that produce IL-17 (Th17 cells) during immunoinflammatory events. In addition to discussing studies done in mice to highlight some unresolved issues in the biology of these cells, we emphasize the need to include outbred animals and humans in analyses. Achieving a balance between Treg and Th17 cells responses represents a powerful approach to control events during immunity and immunopathology.
