bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interferon regulatory factor 5 expression in myeloid cells and T cells negatively impacts the outcome of visceral leishmaniasis
Authors: Mai Linh Thuy , Fabié Aymeric , Smans Mélina , Hammami Akil , Stäger Simona 
Published: January 2023

Abstract
Visceral leishmaniasis (VL) is a potentially fatal disease caused by Leishmania donovani and/or L. infantum. VL is characterized by hepatosplenomegaly, immune suppression, and chronic inflammation. We have previously reported that the transcription factor IRF-5 largely contributes to the induction of inflammation and the development of splenomegaly in mice infected with L. donovani. Moreover, Irf5−/− mice only develop limited IFNγ+ CD4 T responses and are more susceptible to infection. However, the cellular source of IRF-5 responsible for these effects is yet unknown. IRF-5 is constitutively expressed in several cells, such as macrophages, B cells, and dendritic cells. We have recently reported that CD4 T cells also express IRF-5 during chronic VL. Here, we investigate IRF-5 function in myeloid and CD4 T cells during VL, using cell-specific knockout mice. First, we show that IRF-5 expression in CD11c+ cells is required for the generation of splenomegaly and leads to increased disease susceptibility. We also demonstrate that IRF-5 expression in CD11c+ cells is not crucial for the development of Th1 responses. Moreover, we demonstrate that IRF-5 activation in Th1 cells results in cell death during chronic L. donovani infection. Triggering of TLR7 by apoptotic cell material promotes IRF-5 activation in Th1 cells. This results in the upregulation of death receptor 5 and caspase 8, making IFNγ+ CD4 T cells more prone to cell death. Because chronic inflammation and tissue disruption are common characteristics of persistent infections, the TLR7- IRF-5 pathway in CD4 T cells may represent a novel mechanism aimed at protecting tissues against sustained inflammation.
Expression of virulence factors and pro-inflammatory cytokines by Candida species associated with Vulvovaginal Candidiasis in Eastern Nigeria
Authors: Emele Felix Emele , Anieto Ezinne Chinelo 
Published: January 2023

Abstract

Introduction
Candida albicans (CA) is a major cause of vulvovaginal candidiasis (VVC). Adherence to vaginal epithelial cells (VECs) is considered the first step in Candida colonization and eventual invasion of the vaginal mucosa; extracellular hydrolytic enzymes play important role in the invasion of the host. Transition from colonizing yeast cells to tissue-invading hyphae results in secretion of pro-inflammatory mediators, such as IFN-γ, IL-1β, and IL-17. Our earlier reports suggested increasing involvement of non-albicans Candida species (NAC) in VVC, in our locality. We, therefore, saw the need to compare local isolates of CA and NAC for virulence potentials and production of key inflammatory cytokines.

Materials and Methods
Isolates of CA and NAC were investigated for proteinase, phospolipase, and haemolytic activity, as well as ability to adhere to vaginal epithelial cells (VECs) of women of Child-bearing age. The isolates were also inoculated (intra-vaginally) into mice, and assayed for IFN-γ, IL-1β, and IL-17.

Results
Production of phospholipase, proteinase, and haemolysis, by the isolates, were as follows: (CA = 57%, 91%, and 100%; NAC = 10%, 83%, and 78%, respectively). Mean adherence to VECs was: NAC (2.90+3.40); CA (2.81+2.0). Comparable levels of cytokines were generated by CA and NAC in vaginal wash and serum, although NAC produced slightly more IL-17 than CA in day 14.

Conclusion
Based on the results, it could be concluded that the increasing prevalence of NAC in VVC could possibly be as a result of increasing immuno-compromising states of women in our locality, rather than etiological factors.
Immune reactivity to tuberculosis and candida antigens in subjects with latent tuberculosis infection and unexposed subjects: A validation cohort study
Authors: Escalante Patricio , Pennington Kelly M. , Van Keulen Virginia P. , Erskine Courtney L. , Peikert Tobias 
Published: January 2023

Abstract

Rationale
Candida albicans (CA) is ubiquitous and individuals are often immunized against it. However, skin testing reactivity with CA-antigens (CAAg) have been variable during latent tuberculosis infection (LTBI) screening. We hypothesized that the use of a CAAg in an ELISPOT assay would provide a positive control to study tuberculosis (TB)-antigen specific immune responses.

Objective
To test an ELISPOT with TB-antigens and control conditions, including a purified protein derivative of CA, CAAg, that differentiates subjects with LTBI from unexposed subjects.

Methods
An ELISPOT that detects interferon-γ from PBMCs (2×105 cells) after 2-day incubation with TB antigens, controls, including CAAg, and co-stimulatory antibodies. We studied two independent cohorts of subjects with LTBI diagnosis based on TST and IGRA results per clinical guidelines.

Results
One-hundred thirty-nine subjects were studied in 2010–12, including 27 patients with LTBI and 21 IGRA(−) unexposed subjects. ELISPOT with TB-antigens but also CAAg - nil (78 [21 – 182] vs. 9 [1 – 50] cfu) differentiated LTBI subjects from unexposed ones (P&lt;0.005). A second cohort of 76 subjects were studied in 2015–17, including 14 patients with LTBI and 24 unexposed controls, which showed similar statistical results. Positive control (SEAB/antiCD3) did not differentiate these study groups. ELISPOT results with CAAg correlated with results of ELISPOT with TB antigens in all subjects (P&lt;0.001), and in the LTBI and unexposed groups independently.

Conclusion
An ELISPOT assay that includes CAAg revealed immune reactivity that is prevalent in LTBI. The immune subsets that react to both CA and mycobacterial antigens are unclear, but may be relevant for both TB and candida immunity.
Investigating Staphylococcus aureus tolerance to innate immunity
Authors: Kluthe Kennedy Elizabeth , Daubert Trevor , Page Alexis , Carlson Kim , Nuxoll Austin 
Published: January 2023

Abstract
S. aureus accounts for approximately 80,000 infections every year, resulting in 11,000 deaths. While antibiotic resistance has been researched heavily, antibiotic tolerance has not. Persister cells are dormant like cells that are tolerant to antibiotic treatment. Persister cells could be the cause of many chronic and relapsing infections. Recent experiments have shown central metabolism is a critical component of persister cell formation. Results suggest that interruptions in the tricarboxylic acid (TCA) cycle increase persister cell formation. While many studies have been performed concerning the mechanism of formation of persister cells, few have been done to analyze how persister cells react in in vivo models or against aspects of the innate immune system. Antimicrobial peptides (AMPs) are a key component of the innate immune system. Challenging wild type S. aureus with AMPs, LL-37 and hBD-3, showed several logs of killing. Interruption of the TCA cycle (fumC) resulted in 100-fold more surviving cells compared to wild type. Following infection in Drosophila melanogaster, the fumC knockout exhibited increased survival. Furthermore, D. melanogaster that were infected with fumC had reduced survival. Interruption of the TCA cycle also led to increased survival within a macrophage suggesting persister cells represent a multifaceted problem for the immune system. These data suggest that persisters not only present a challenge during antimicrobial therapy but also for the innate immune system.
Polymicrobial sepsis impairs antigen-specific memory CD4 T cell-mediated immunity
Authors: Sjaastad Frances V , Kucaba Tamara A , Dileepan Thamotharampillai , Swanson Whitney , Dail Cody S , Cabrera-Perez Javier , Murphy Katherine A , Badovinac Vladimir P , Griffith Thomas S 
Published: January 2023

Abstract
Sepsis strikes 750,000 Americans annually. Patients who survive sepsis display prolonged immune dysfunction and heightened risk of secondary infection. CD4 T cells support a variety of cells required for protective immune responses, and perturbations to the CD4 T cell compartment can decrease overall immune system fitness. Using the cecal ligation and puncture (CLP) mouse model of sepsis, we investigated the impact of sepsis on endogenous Ag-specific memory CD4 T cells generated in C57Bl/6 (B6) mice infected with attenuated Listeria monocytogenes (LM) expressing the I-Ab-restricted 2W1S epitope (LM-2W). Sepsis transiently reduced the number of 2W1S-specific memory CD4 T cells on day 2, but numbers recovered by day 14. In contrast to the transient numerical change, there was prolonged impairment in the functional capacity of the 2W1S-specific memory CD4 T cells after sepsis, evidenced by a reduced recall response (proliferation and effector cytokine production) after restimulation with cognate Ag. We then assessed 2W1S-specific memory CD4 T cell-mediated protection to a secondary bacterial challenge after sepsis induction. B6 mice were infected with attenuated Salmonella-2W 30 days before sham or CLP surgery, and then challenged with virulent Salmonella-2W after surgery. Pathogen burden was significantly higher in the CLP-treated mice compared to shams. Similar reductions in functional capacity were noted for the endogenous OVA323–339-specific memory CD4 T cell population in septic mice. Our data collectively show CLP-induced sepsis alters the number and function of Ag-specific memory CD4 T cells, which contributes (in part) to the characteristic long-lasting immunoparalysis seen after sepsis.
Activation of skin-resident group 2 innate lymphoid cells by cold-sensing TRPM8+ neuron-derived signals in thermo-homeostatic regulation and tissue inflammation
Authors: Xu Ming 
Published: January 2023

Abstract
Innate lymphoid cells (ILCs) in the skin are a heterogeneous population of innate lymphocytes that function in local homeostatic regulation but could also cause inflammation. How homeostatic versus inflammatory functions of skin ILCs are regulated is poorly understood. To explore this question, we analyzed gene expression profiles of skin ILCs of wild-type and Rag1−/− mice and discovered that the chemokine receptor CCR10+ skin ILCs dominant in the health skin were of homeostatic properties while CCR10− skin ILCs are activated effector cells with elevated expression of various stimulatory cytokine receptors and signaling molecules. In stearoyl-CoA desaturase 1-knockout (KO) mice whose skin was defective in thermohomeostatic maintenance due to impaired fatty acid synthesis and lipid barrier formation, there was predominant activation of CCR10−CD81+ST2+ group 2 ILCs (ILC2s) while raising these mice at a thermo-neutral room temperature or feeding them with high-fat diet reduced the ILC2 activation, suggesting that skin ILC2s are activated by cold-induced signals to help thermo-homeostatic maintenance. Consistent with this, topical application of menthol, an agonist ligand for the cold-sensing receptor TRPM8, led to activation of CCR10−CD81+ST2+ skin ILC2s and increased dermal adipocyte maturation and uncoupling protein 1 production. Furthermore, compared to wild-type controls, menthol-treated TRPM8-KO and IL-18-KO mice had reduced CCR10−CD81+ activated skin ILC2s, suggesting that IL-18 mediated the TRPM8 activation of skin ILC2s. Our study reveals a neuron-derived cold-sensing pathway in activation of skin ILC2s that helps thermo-regulation but could also cause tissue inflammation if chronically activated.
Migratory memory CD4 T cells surveilling the lower reproductive tract direct rapid clearance of Chlamydia muridarum following vaginal challenge
Authors: Kohlmeier Alison , Li Tiger , Lobby Jenna , Kost Kirsten , Dunbar Paul , Lowen Anice , Zheng HaoQiang , Kohlmeier Jacob E 
Published: January 2023

Abstract
Despite their importance for immunity against sexually transmitted infections, the regulation and function of CD4 T cells in the female reproductive tract (FRT) remains poorly defined. Here we show that across human, non-human primate, and mouse species the FRT memory CD4 T cell pool consists of distinct subsets corresponding to migratory (TMM) and resident (TRM) memory T cells. TMM in the FRT exhibit broad expression of trafficking molecules, restricted distribution to discreet areas of the FRT, and differential responses to local infection. To investigate the contribution of TMM to protective immunity in the FRT, we constructed an influenza virus (HK/x-31) expressing an immunodominant CD4 T cell epitope from the Chlamydia muridarum probable outer membrane protein (PmpG-1303–311). C57Bl/6 mice were infected intranasally with x31-PmpG1 to generate PmpG1-specific CD4 TMM and investigate their ability to surveil distant mucosal tissues. PmpG1-specific CD4 T cells were found restricted into the lower, but not upper, FRT and expressed chemokine receptors and adhesion molecules consistent with TMM. Vaginal challenge of x31-PmpG1 memory mice with C. muridarum showed a significant decrease in bacterial burden at 14 days post-infection (dpi), when bacterial clearance was first detectable in naïve control mice. Notably, x31-PmpG1 memory mice treated with FTY720 during the initial stages of C. muridarum challenge failed to limit bacterial growth, suggesting this effect was due in part to TMM localization to the FRT. These data show that vaccinating at distant mucosal sites can generate surveilling CD4 TMM cells that are distinct from classical central, effector and resident memory CD4 T cells, and can protect against pathogens in the FRT.
The role of CCL27 in the establishment, maintenance, and homeostasis of skin-resident CCR10+ lymphocytes
Authors: Davila Micha L , Xiong Na 
Published: January 2023

Abstract
The skin hosts an array of immune cell populations that are important for maintaining local tissue integrity; dysregulation of these cells can lead to inflammatory diseases such as psoriasis and atopic dermatitis. Understanding how skin-resident immune cells are regulated is important in the effort to treat skin diseases. The majority of skin-homing and skin-resident lymphocytes express the chemokine receptor CCR10. Our lab has found that CCR10 is important for the homeostatic establishment of skin-resident lymphocytes. The skin-specific ligand of CCR10 is CCL27, a chemokine primarily expressed by keratinocytes. While the regulation and functions of CCL27 are not well understood we have found evidence to suggest that CCL27 has a homeostatic role in the skin. We report that CCL27 expression in keratinocytes and within regions of cycling hair follicles is developmentally regulated, independent of commensal bacterial stimulation. Further, CCL27 expression correlates with the localization of CCR10+ lymphocytes to specific regions within the skin. Newly generated CCL27-knockout mice show that the loss of CCL27 results in the diminished migration and localization of CCR10+ lymphocytes into the skin, particularly within regulatory and CD8+ T cell populations. Preliminary data also indicates CCL27-knockout mice had more severe skin inflammation than wild-type mice in a model of psoriasis. These findings reveal that the regulation of CCL27 expression is important for directing the localization of CCR10+ lymphocytes to specific niches of the skin, helping to maintain local homeostasis under steady-state conditions and hair follicle cycling, and that the loss of CCL27 may contribute to inflammatory diseases.
IL17 and Candida albicans colonization in the vaginal mucosa
Authors: Coleman Bianca M , Peters Brian M , Willems Hubertine M.E. , Barker Katherine S. , Aggor Felix E.Y. , Cipolla Ellyse , Verma Akash H , Bishu Srinivas , Huppler Anna H , Bruno Vincent M , Childs Erin E , Conti Heather , Gaffen Sarah L 
Published: January 2023

Abstract
Candida albicans is a ubiquitous commensal fungus that colonizes human mucosal tissues. C. albicans can become pathogenic, clinically manifesting most commonly as oropharyngeal, dermal or vulvovaginal candidiasis (VVC). Studies in mice and humans convincingly show that Th17/IL-17-driven immunity is essential to controlling oral and dermal candidiasis. In contrast, the role of the IL-17 pathway during VVC remains controversial, with conflicting reports from human data and mouse models. It has been observed that a strong IL-17-related gene signature is induced in the vagina during estrogen (E2)-dependent murine VVC. IL-17R deficient mice are resistant to VVC in this standard model of E2-induced disease. Since estrogen increases susceptibility to vaginal colonization and subsequent immunopathology, first we asked whether its use in the standard VVC model masks a role for the Th17/IL-17 axis. Here, we demonstrate that mice lacking IL-17 receptor signaling showed no evidence for altered VVC susceptibility or immunopathology, regardless of estrogen administration, supporting the emerging consensus that Th17/IL-17 axis signaling is dispensable for the immunopathogenesis of VVC. We further considered the epithelial dynamics during murine VVC. C. albicans colonizes mucosal epithelial tissues, particularly those expressing Keratin 13 (K13). When estrogen levels are high, this epithelium becomes increasingly keratinized, characterized by a thick layer of thin, flat pieces of tissue. In order to visualize the expression patterns in the vaginal epithelium, we developed a reporter mouse where LACZ is expressed in all tissues containing K13. We present data using these mice to assess epithelial dynamics during VVC.
Cigarette Smoke Induces Intestinal Inflammation via a Th17 Cell-Neutrophil Axis
Authors: Kim Myunghoo 
Published: January 2023

Abstract
Epidemiological evidence finds cigarette smoking is a common risk factor for a number of diseases, not only in the lung but also in other tissues, such as the gastrointestinal tract. While it is well-documented that smoking directly drives lung inflammatory disease, how it promotes disease in peripheral tissues is incompletely understood. In this study, we utilized a mouse model of short-term smoke exposure and found increased Th17 cells and neutrophilia in the lung as well as in the circulation. Following intestinal inflammatory challenge, smoke exposed mice showed increased pathology which corresponds to enhanced intestinal Th17 cells, ILC3 and neutrophils within intestinal tissue. Using cellular depletion and genetic deficiencies, we define a cellular loop by which IL-17A and downstream neutrophils drive cigarette smoke-enhanced intestinal inflammation. Collectively, cigarette smoke induced local lung Th17 responses lead to increased systemic susceptibility to inflammatory insult through enhanced circulating neutrophils. These data demonstrate a cellular pathway by which inflammatory challenge in the lung can sensitize the intestine to enhanced pathological innate and adaptive immune responses
Revisiting the critical role of Th17 cell plasticity in the Peyer’s patch for gut IgA responses using single cell analysis unexpectedly demonstrated unperturbed responses to oral immunization in their complete absence
Authors: Lycke Nils , Gribonika Inta , Bemark Mats 
Published: January 2023

Abstract
Gut Th17 cells are present at the Peyer’s patch inductive site as well as at the lamina propria effector site of the intestinal immune system. These cells are responsive to pathogens as well as to the commensal microbiota and they appear to be critical for gut homeostasis. While they have been associated with immune protection against pathogens they are also known to drive autoimmune inflammation in the gut. Hence, plasticity is a hallmark of gut Th17 cells and pro- as well as anti-inflammatory functions can be expected. This places Th17 cells at center stage for immune regulation of the gut immune system. However, their role for gut IgA responses to oral immunization awaits to be better defined, although earlier studies suggested that Th17 cells play a central role as their plasticity can convert them into follicular helper T (Tfh) cells that stimulate IgA class-switching and drive gut IgA responses. Here we used an IL-17 fate-reporter mouse and a cholera toxin B-subunit (CTB)-specific tetramer to isolate CTB-specific CD4 T cell subsets following oral immunization with CT. We found no evidence of CTB-specific Th17 development in the PP, rather a clear dominance of Tfh cells was observed. Single-cell RNAseq analysis revealed a massive clonotypic dominance of Tfh cells, but no Th17 or regulatory T cells (Tregs) were found among the CTB-tetramer-specific CD4 T cells. While 3 clusters of Tfh cells were found only one cluster hosted the CTB-specific CD4 T cells. An adoptive transfer of rorgt-deficient CD4 T cells into nu/nu recipient mice exhibited unperturbed gut IgA responses to oral CT immunization, clearly demonstrating that Th17 cells are, indeed, dispensible for gut IgA responses following oral immunization.
The role of glutamate-NMDA-receptor in mice alpha beta T cells from intestinal mucosa
Authors: De Oliveira Marília Garcia , Andreoni Rafaela , Brandao Wesley , Peixinho Beatriz , Polonio Carolina Manganeli , Zanluqui Nagela Ghabdan , Oliveira Lilian , Peron Jean Pierre S 
Published: January 2023

Abstract
The intestinal mucosa consists of a simple layer of epithelial tissue and loose connective tissue called the lamina propria that is formed by several immune cells mainly T cells that play important roles in local tolerance to microorganisms of the microbiota and food antigens. In addition to mucosa the small and large intestines also present the submucosal and the muscular layers that present ganglionic enteric plexuses formed by networks of interconnection between autonomic neurons of the enteric nervous system. These neurons secrete various neurotransmitters including glutamate and their innervations reach the lamina propria. It is known that T cells have receptors for neurotransmitters even the ionotropic glutamate receptor NMDAR. Thus, the present study intends to evaluate the role of NMDAR in αβ T cells from intestinal mucosa. C57BL/6 Grin1f/f and CD4crexGrin1flox mice of both sexes were used at 8 weeks of age. CD4+ T cells, CD8+ T cells, γδT cells, dendritic cells and macrophages present in mesenteric lymph nodes and at intraepithelial compartment of small intestine were evaluated. We found that CD8+ T cells were decreased and γδT cells were increased in mesenteric lymph nodes of CD4crexGrin1flox mice in comparison to the control group. Thus, intraepithelial CD4+ T cells and macrophages were increased, but intraepithelial CD8+ T cells were decreased in small intestine of CD4crexGrin1flox mice compared to the control group. Our preliminary results shows that the absence of NMDAR exclusively in αβ T cells alters the percentage of immune cells present both in mesenteric lymph nodes and intraepithelial compartment of small intestine suggesting a modulation by glutamate. New evaluations are still in progress to better understand that.