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There is increasing evidence of a close link between inflammation and cancer, and at the core of inflammation there are both pathogen‐associated molecular patterns (PAMPs) and danger (or damage)‐associated molecular patterns (DAMPs). Microorganisms harbor molecules structurally conserved within groups called PAMPs that are recognized by specific receptors present on immune cells, such as monocytes and dendritic cells (DCs); these are the pattern recognition receptors (PRRs). Activation through different PRRs leads to production of pro‐inflammatory cytokines. A robust immune response also requires the presence of endogenous molecules that pose ‘danger’ to self‐tissues and are produced by damaged or stressed cells; these are the DAMPs, which act also as inducers of inflammation. PAMPs and DAMPs are each recognized by a limited set of receptors that in number probably do not exceed 100. PAMPs and DAMPs interact with each other, and a single PRR can bind to a PAMP as well as a DAMP. Within this framework, we propose that PAMPs and DAMPs act in synchrony, modifying the activation threshold of one another. Thus, the range of PAMP–DAMP partnerships defines the course of inflammation, in a predictable manner, in an ‘inflammatory code’. The definition of relevant PAMP–DAMP complexes is important for the understanding of inflammatory disorders in general, and of cancer in particular. Here, we review relevant findings that support the notion of a PAMP–DAMP‐based inflammatory code, with emphasis on cancer immunology and immunotherapy.

During pregnancy, the placenta, the mother and the fetus exploit several mechanisms in order to avoid fetal rejection and to maintain an immunotolerant environment throughout nine months. During this time, immune cells from the fetal and maternal compartments interact to provide an adequate defense in case of an infection and to promote a tolerogenic milieu for the fetus to develop peacefully. Trophoblasts and decidual cells, together with resident natural killer cells, dendritic cells, Hofbauer cells and other macrophages, among other cell types, contribute to the modulation of the uterine environment to sustain a successful pregnancy. In this review, the authors outlined some of the various roles that the innate immune system plays at the maternal–fetal interface. First, the cell populations that are recruited into gestational tissues and their immune mechanisms were examined. In the second part, the Toll–like receptor (TLR)–dependent immune responses at the maternal–fetal interface was summarized, in terms of their specific cytokine/chemokine/antimicrobial peptide expression profiles throughout pregnancy.

The close interaction between fetal and maternal cells during pregnancy requires multiple immune-endocrine mechanisms to provide the fetus with a tolerogenic environment and protection against any infectious challenge. The fetal membranes and placenta create a hyperprolactinemic milieu in which prolactin (PRL) synthesized by the maternal decidua is transported through the amnion-chorion and accumulated into the amniotic cavity, where the fetus is bedded in high concentrations during pregnancy. PRL is a pleiotropic immune-neuroendocrine hormone with multiple immunomodulatory functions mainly related to reproduction. However, the biological role of PRL at the maternal-fetal interface has yet to be fully elucidated. In this review, we have summarized the current information on the multiple effects of PRL, focusing on its immunological effects and biological significance for the immune privilege of the maternal-fetal interface.

The HIV epidemic remains a major public health challenge, specifically for women living with HIV who face vulnerabilities during pregnancy and motherhood. Furthermore, high vulnerability is closely linked to a lower quality of life. It is essential to address the determinants that influence quality of life within this population in order to enhance health outcomes and inform the development of evidence-based care protocols. An observational, cross-sectional study was conducted from 2020 to 2022 to assess the quality of life of Mexican postpartum women living with HIV (n = 75). The WHOQoL-HIV-Bref instrument was used. Quality of life results were analysed statistically in relation to sociodemographic and clinical factors to evaluate their associations and their predictive power through multinomial logistic regression analysis. Nearly half of postpartum WLWH experienced a lower quality of life (49%). Psychological health, Environment, Spirituality, religion and personal beliefs domains scores were below the median. There were multiple associations with socio-demographic and clinical factors. Highlights the use of ART during pregnancy and postpartum, HIV symptoms, sexual behavior, marital and educational status, mainly. Physical health, Independence level, and Spirituality, religion and personal beliefs domains were identified as potential predictors of a perception of high quality of life of this population. There are clinical and socio-demographic factors that influence the perception of quality of life in Mexican women living with HIV during postpartum. It is important to identify and mitigate these factors for the well-being of these women and their children. Further research is needed to evaluate the impact of interventions on Physical health, Independence level, and Spirituality, religion and personal beliefs domains to improve perception of high quality of life in WLWH. These findings ultimately underscore the need to integrate quality of life assessment as the fourth '95' target in World Health Organization strategies for people living with HIV.

The success of human pregnancy relies on the precise synchronization and adaptation of the maternal immune system, which, together with fetal tissues, establishes a tolerogenic intrauterine environment while maintaining the capacity to mount effective immune responses. At the maternal–fetal interface, multiple physical and immune mechanisms coordinate the recognition and control of pathogens that could jeopardize pregnancy. Ascending infections from the lower genital tract can reach the uterine cavity, infect the fetal membranes (chorioamnionitis), and invade the amniotic fluid, triggering a proinflammatory response strongly associated with adverse outcomes. Both maternal and fetal compartments deploy several defense strategies, among which antimicrobial proteins and peptides (AMPs) play a central role. These small, pleiotropic molecules, produced mainly by epithelial surfaces and inflammatory cells, exhibit broad-spectrum antimicrobial and immunomodulatory activities, constituting a key component of the first line of defense at the maternal–fetal interface. This review summarizes the principal AMPs produced by the placenta, fetal membranes, decidua, maternal reproductive tract, and fetal tissues, describes their mechanisms of action, factors regulating their expression, and explores their role in both physiological and pathological processes.

Background Cytokine levels have been extensively described in pregnant subjects under normal and pathological conditions, including mood-related disorders. Concerning chemokines, very few studies have reported their association with psychiatric disorders during pregnancy. Therefore, we explored the chemokine profile in women exhibiting anxiety and depression during late pregnancy in the present study. Methods One hundred twenty-six pregnant women in the 3rd trimester of pregnancy, displaying moderate to severe anxiety (ANX) alone and women exhibiting moderate to severe anxiety with comorbid depression (ANX + DEP), and 40 control pregnant women without affective disorders (CTRL) were evaluated through the Hamilton Anxiety Rating Scale (HARS) and the Hamilton Depression Rating Scale (HDRS). Serum chemokine levels of MCP-1 (CCL2), RANTES (CCL5), IP-10 (CXCL10), Eotaxin (CCL11), TARC (CCL17), MIP-1α (CCL3), MIP-1β (CCL4), MIG (CXCL9), MIP-3α (CCL20), ENA-78 (CXCL5), GROα (CXCL1), I-TAC (CXCL11) and IL-8 (CXCL8)] were measured by immunoassay. Clinical, biochemical, and sociodemographic parameters were correlated with HARS and HDRS score values. Results Serum levels of most chemokines were significantly higher in the ANX and in the ANX + DEP groups, when compared to the CTRL group. Positive correlations were observed between MIP-1α/CCL3, MIP-1β/CCL4, MCP-1/CCL2, MIP-3α/CCL20, RANTES/CCL5, Eotaxin/CCL11, and I-TAC/CXCL11 with high scores for anxiety (HARS) ( p  < 0.05) and for depression (HDRS) ( p  < 0.004). After controlling clinical measures for age + gwk + BMI, chemokines such as IL-8/CXCL8, MCP-1/CCL2 and MIP-1β/CCL4 were found associated with high scores for anxiety ( p  < 0.05) in the ANX group. TARC/CCL17 and Eotaxin/CCL11 showed significant associations with high scores for depression ( p  < 0.04) whereas, MCP-1/CCL2 and MIP-1α/CCL3 were significantly associated with high scores for anxiety ( p  < 0.05) in the ANX + DEP group. Using a multivariate linear model, high serum levels of MIP-1β/CCL4 and Eotaxin/CCL11 remained associated with depression ( p  < 0.01), while, IL-8/CXCL8, MIP-1β/CCL4, MCP-1/CCL2, and MIP-1α/CCL3 were associated with anxiety ( p  < 0.05) in the symptomatic groups. Conclusions Our data show that serum levels of distinct chemokines are increased in women exhibiting high levels of affective symptoms during late pregnancy. Our results suggest that increased levels of anxiety, depressive symptoms, and mood-related disorders may promote changes in specific functional chemokines associated with a chronic inflammatory process. If not controlled, it may lead to adverse obstetric and negative neonate outcomes, child development and neuropsychiatric alterations in the postnatal life. Highlights Chemokine levels increase in affective disorders during pregnancy .

Elevated glucose levels during pregnancy disrupt placental structure, signaling, and cellular interactions, impairing its immune response. In mothers with gestational diabetes mellitus (GDM), (Group B , GBS) is the second leading cause of bacterial infections. GDM is also linked to altered chemokine profiles in maternal serum and placenta tissue. However, the impact of hyperglycemia on placental immune responses to bacterial infections remains poorly understood. This work aimed to evaluate cytokine and chemokine production, as well as chemotactic responses, in the placenta following GBS infection under hyperglycemic conditions. Human villous explants from term, normoevolutive pregnancies were cultured with 5, 10 or 50 mM glucose, and subsequently infected or not with GBS. Bacterial growth and adherence to villous tissue, syncytial disruption, cytokine and chemokine mRNA expression and secretion, leukocyte chemotaxis using intervillous blood mononuclear cells (IVMC), and TLR-2 expression at both mRNA and protein levels, were evaluated. Under high glucose conditions, GBS showed increased proliferation and invasiveness, while villous explants presented evidence of syncytial barrier degradation. Also, placental TNF-α, MCP-1, and MIP-1β were induced by GBS infection. However, the dual challenge of high glucose and infection reduced the above inflammatory markers' gene and protein synthesis. GBS infection enhanced IVMC migration compared to uninfected groups, but the combination of GBS and hyperglycemia led to a reduced migration of IVMC, particularly monocytes and NK cells. TLR-2 placental expression was also downregulated by this dual challenge. At the placental level, hyperglycemia attenuates the immune response against GBS infection, promoting syncytial disruption, bacterial growth, and tissue colonization. The combined stimulus of hyperglycemia and GBS resulted in reduced placental expression of TLR-2, TNF-α, MCP-1, and MIP-1β, thereby impairing the chemotaxis of IVMC, monocytes, and NK cells. This dysregulated immune response may compromise bacterial clearance and placental integrity, favoring pathogen persistence. Our findings suggest a potential mechanism by which hyperglycemia increases susceptibility to GBS-associated complications, offering novel insight into the interplay between metabolic and infectious stressors at the maternal-fetal interface.

Breast milk is the primary source of nutrients, bacterial, and defensive elements, which are required for infants in their first years of life. Colostrum, the first stage of breast milk, contains abundant levels of antibodies, lymphocytes, and commensal bacteria. The affinity, phenotype, and diversity of these components resemble those found in maternal enteric mucosa, suggesting that the enteromammary pathway facilitates their transport. In the gut, commensal bacteria, IgA, and regulatory T cells (Treg) are interrelated in maintaining immune tolerance and defense, leading us to hypothesize that similar correlations may exist in colostrum. In this study, we present a descriptive analysis of 33 colostrum samples collected from healthy women. DNA from Staphylococcus, Streptococcus, Bifidobacterium, Lactobacillus, and Enterococcus was quantified by quantitative PCR (qPCR). Immunoglobulin isotypes and cytokines were measured using multiplex immunoassays, and the Treg cell frequencies were determined by flow cytometry. Correlation tests and multivariate analysis were used to evaluate these associations. The results showed that Streptococcus and Staphylococcus, common bacteria found on the skin and predominantly in breast milk, were not significantly associated with immunoglobulins or Treg cells. Interestingly, Bifidobacterium, but not Lactobacillus or Enterococcus, showed a positive correlation with Treg cells. Contrary to our initial hypothesis, neither Treg cells or Bifidobacterium were negatively correlated with antibodies. These findings suggest a potential association between Treg cells and specific commensal bacteria, particularly Bifidobacterium, that appears to be independent of immunoglobulins. This cellular microbial interaction could be involved in neonatal gut colonization, immune tolerance, and early immune responses to antigenic challenges.

Cervical ectopy is a benign condition of the lower genital tract that is frequently detected in women of reproductive age. Although cervical ectopy is regarded as a physiological condition, some women experience symptoms such as leucorrhoea, persistent bleeding and recurrent vaginal infections that require medical intervention. Cervical ectopy has not been linked to cervical cancer, but it is thought to facilitate the acquisition of sexually transmitted diseases (STDs), like Human Papillomavirus (HPV) infection, as it provides a favorable microenvironment for virus infection and dissemination. We and others have described the presence of oncogenic HPV types in women with symptomatic cervical ectopy. The relevance of this finding and the impact of symptomatic cervical ectopy on the cervicovaginal microenvironment (vaginal microbiota, immune and inflammatory responses) are currently unknown. To shed some light into the interplay between HPV, the vaginal microbiota and mucosal immune and inflammatory responses in the context of this condition, we enrolled 156 women with symptomatic cervical ectopy and determined the presence of HPV using a type-specific multiplex genotyping assay. Overall, HPV was detected in 54.48% women, oncogenic HPV types were found in more than 90% of HPV-positive cases. The most prevalent HPV types were HPV16 (29.4%), HPV31 (21.17%) and HPV18 (15.29%). Next, we evaluated the vaginal microbial composition and diversity by 16S rDNA sequencing, and quantified levels of cytokines and chemokines by flow cytometry using bead-based multiplex assays in a sub-cohort of 63 women. IL-21 and CXCL9 were significantly upregulated in HPV-positive women ( p =0.0002 and p =0.013, respectively). Women with symptomatic cervical ectopy and HPV infection had increased diversity ( p <0.001), and their vaginal microbiota was enriched in bacterial vaginosis-associated anaerobes ( Sneathia , Shuttleworthia , Prevotella , and Atopobium ) and depleted in Lactobacillus spp. Furthermore, the vaginal microbiota of women with symptomatic cervical ectopy and HPV infection correlated with vaginal inflammation (IL-1β, rho=0.56, p =0.0004) and increased mucosal homeostatic response (IL-22, rho=0.60, p =0.0001). Taken together, our results suggest that HPV infection and dysbiotic vaginal communities could favor a vaginal microenvironment that might delay the recovery of the cervical epithelium in women with symptomatic cervical ectopy and favor STDs acquisition.

Mono(2-ethylhexyl) phthalate (MEHP), a bioactive metabolite of di(2-ethylhexyl) phthalate (DEHP), has been detected in the placenta and urine of pregnant women and is linked to adverse pregnancy outcomes. However, its effects on mitochondrial homeostasis in trophoblast cells remain incompletely understood. This study examined the impact of MEHP (0.5–200 µM) on mitochondrial function, dynamics, and biogenesis in human HTR-8/SVneo trophoblast cells. MEHP (≥5 µM) reduced MTT conversion without compromising membrane integrity, suggesting early metabolic or redox imbalance. A dose-dependent loss of mitochondrial membrane potential was observed, with increased reactive oxygen species (ROS) generation only at 200 µM. MEHP modulated the expression of mitochondrial dynamics genes, with a more pronounced mitofusin 1 (MFN1) induction at low doses and increased mitochondrial DNA content, suggesting a compensatory response to mild stress. Conversely, high doses more strongly induced fission and mitochondrial 1 (FIS1) expression, suggesting mitochondrial fragmentation. Both concentrations induced the expression of the mitochondrial biogenesis regulators peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) and nuclear factor erythroid 2–related factor 2 (Nrf2), while sirtuin 1 (SIRT1) expression and activity declined progressively with dose. These results demonstrate that MEHP disrupts mitochondrial homeostasis in trophoblast cells at concentrations spanning the estimated human exposure range. The dose-dependent effects, from adaptive responses to overt dysfunction, may help explain the associations between MEHP exposure and placental pathology observed in epidemiological studies.