bluuebunny/crossref_metadata_2025_split huggingface dataset:
Host Transcriptome Studies in Response to Feline Coronavirus Reveal Differences in Macrophages vs CRFK
Authors: Drechsler Yvonne , Vasconcelos Elton JR , Diniz Pedro PVP 
Published: January 2023

Abstract
Feline coronavirus (FCoV) is a highly contagious virus that exists as two pathotypes, with feline infectious peritonitis (FIP) caused by the pathogenic FIPV. The pathogenesis of FIPV strains remains an enigma, and several different theories are still being discussed. A predominant theory has been that the pathogenic FIPV arises from a mutation of the enteric form, so that it could replicate not only in enterocytes of the intestines but also in monocytes, which subsequently transported the virus systemically. A strong argument can also be made for a role of the immune status and genetics of affected cats in pathogenesis. While some studies have looked at ex vivo infection of macrophages with virulent and avirulent strains, most of these studies focus on viral entry or differential replication instead of host responses. Considering the importance of genetics and host immune responses in viral infections, transcriptome studies to elucidate host pathogen interactions in macrophages and CRFK at different time points were performed by next-generation sequencing of mRNA. CRFK and macrophages from healthy male cats infected with FIPV 79-1146 ex vivo displayed differential gene expression in response. While CRFK gene expression was enriched for many classical virally induced genes and pathways, gene expression in macrophages was quite different. Instead, macrophage responses were very individual and showed limited overlap among cats. Interestingly, some of the commonly downregulated genes in macrophages involved innate anti-viral factors, while upregulated genes fell within unexpected pathways, such as autophagy, cellular senescence and other cellular processes not directly linked to infection.
The emergence and evolution of the mammalian germinal center: analysis of the splenic microarchitecture of the teleost threespine stickleback (Gasterosteus aculeatus)
Authors: Steinel Natalie C , Vaidyanathan Saraswathy 
Published: January 2023

Abstract
Lymphoid cell-based adaptive immunity first arose in jawed fish ~500 mya and fish lymphoid cells share many conserved features with their mammalian counterparts. Both fish and mammalian B cells respond to T-dependent antigen by proliferating, differentiating into plasma cells, and generating high-affinity, antigen-specific antibody. In mammals, this response occurs in the germinal center (GC) and is highly dependent on GC architecture and cellular dynamics, which direct B cell SHM and clonal selection. Though most cellular components are conserved, little is known with regard to the immune architecture of the fish humoral adaptive response. Therefore, we sought to investigate the organization of B cell activation within the lymphoid tissues of the fish, threespine stickleback (Gasterosteus aculeatus). Stickleback splenic B cells are organized around melanomacrophages (MM), highly pigmented melanomacrophages which are proposed homologues to mammalian follicular dendritic cells (FDCs). We find that MM aggregates, known as melanomacrophage centers (MMCs), increase in size in response to immunization, but not control injection with adjuvant alone, suggesting that the MMC response is antigen driven. Analysis of lymphoid tissue architecture indicates B and T lymphocytes inhabit distinct regions of the stickleback spleen. For instance, IgM mRNA-expressing cells aggregate in discrete regions surrounding MMC clusters, comparable to the organization of mammalian B cells around FDCs. These findings support the hypothesis that MMCs are evolutionary precursors to GCs. Furthermore, it suggests that the microarchitecture necessary to sustain somatic hypermutation and clonal selection evolved early in vertebrates.
A bursa of Fabricius structural analogue in the teleost fish Atlantic salmon
Authors: Bjoergen Haavard , Løken Oskar Mongstad , Hordvik Ivar , Koppang Erling Olaf 
Published: January 2023

Abstract
Knowledge of the construction of immune organs of different species is important to understand the evolution of immunity. In birds, the bursa of Fabricius is a cloaca-based lymphoid organ that has been vital for our current understanding of the adaptive immune system of vertebrates. So far, this structure has not been described in other species. Here, we show a substantial lymphoepithelial tissue in a previously undescribed bursa in the Atlantic salmon, situated analogous to the placement of the avian bursa of Fabricius, also developing from the ectoderm. Investigations of three different age groups of Atlantic salmon revealed a dynamic lymphoepithelium that regressed following sexual maturation. This is similar to the situation in birds. Morphological investigations including dissection, radiography, in situ hybridization and immunohistochemistry revealed presence of T and B cells embedded within a CCL19-positive lymphoepithelium. CCL19 expression is indicative for lymphoid organs, and thus we suggest that the salmonid bursa should be regarded as such. We found however no evidence for primary lymphoid organ functions including recombination events in the lymphocytes, this contrasting the situation in birds. Our results demonstrate the presence of a salmonid lymphoepithelial compartment with anatomical and developmental similarities to early stages in the organogenesis of the avian bursa of Fabricius. Such information provides novel and exciting possibilities both for our understanding of the function of the immune system in salmon and for our understanding of the development of lymphoid structures and niches in vertebrates.
Immune genomic response associated with preference behavior: an examination in a freshwater fish
Authors: Price Sarah , Schumer Molly , Young Rebecca L. , Wang Silu , Cummings Molly 
Published: January 2023

Abstract
Immune activity in the brain underlies many social behaviors. This immune-behavior relationship can be viewed under a genomics scope by isolating transcriptomic correlates and molecular pathways present following various social encounters. Here we explore how immune genes correlate with different social exposures: mate-choice and social affiliation. Using an established model for sexual selection studies, we compared the immune gene responses in female brains following exposure to either a potential mate or a conspecific female. Females from the Poeciliidae family of fishes, the sailfin molly (Poecilia latipinna), were profiled for their social preference behavior and brain transcriptomes using RNA-seq. During the 30 minute behavioral assay, females were placed into one of two groups: (n=8) given the choice of a large male and small male (‘mate choice’) or a choice between a large and small female (n=8; ‘social affiliation’). The relationship between immune gene responses (categorized using Gene Ontology analysis) and behavior (preference, social affiliation, activity) will be explored using a linear model approach for differential expression (limma; Ritchie ME, et al, 2015) and WGCNA (weighted gene co-expression network analysis; Langfelder & Horvath, 2008). The RNA-seq transcriptomes from each female (n=16) will be analyzed by comparing differential expression between the two groups (‘mate-choice’ vs ‘social preference’).
Mycobacterium avium subspecies paratuberculosis (MAP) promotes expression of Th17 related cytokines in bovine CD4+ and CD8+ T cells in the presence and absence of antigen-presenting cells
Authors: Coussens Paul M. 
Published: January 2023

Abstract
The overall purpose of work to be presented was to further examine the potential role of Th17 immune responses and expression of Th17 related cytokines in Johne’s disease (JD). JD is a chronic inflammatory gastrointestinal disease of ruminants caused by Mycobacterium avium subspecies paratuberculosis (MAP). Recently, it has become clear that Th17 immune responses may play a protective role in early mycobacterial infections, but could also contribute to inflammation in later disease. Detection of MAP infection by current immunological methods at early stages of JD is difficult. In addition, correlates of protection are not well known in model systems of JD, complicating vaccine development efforts. Finally, the sources of inflammation in late-stage JD are not well characterized. We have proposed that robust Th17 responses to MAP may help improve upon detection, vaccine development, and control efforts. We have shown that MAP antigens induce mRNAs encoding the Th17 associated cytokines IL-17A, IL-17F, IL-22, IL-23, IL-27, and IFNγ in co-cultures of CD3+ T cells and monocyte derived macrophages (MDMs). Although not as robust as when co-cultured with MDMs, MAP is able to stimulate the upregulation of these cytokines from sorted CD3+ T cells in the absence of APCs. CD4+ and CD8+ T cells are the main contributors of IL-17A and IL-22 in the absence of APCs. However, MAP stimulated MDMs are the main contributor of IL-23. In-vivo, JD+ cows have more circulating IL-23 than JD- cows, suggesting this proinflammatory cytokine could be an important factor in clinical JD. Our data suggests that Th17-like cells and associated cytokines may indeed play an important role in immune responses to MAP infection and development or control of JD.
CD4+ T cell recognition of haemagglutinin epitope across Influenza strains
Authors: Nguyen Andrea T , Sloane Hannah , Grant Emma , Szeto Christopher , Jayasinghe Dhilshan , Gras Stephanie 
Published: January 2023

Abstract
In 2018 the World Health Organisation listed influenza pandemics as one of the top threats to global health. Influenza pandemics occur as a result of the emergence of antigenically distinct strains, which arise due to genomic re-assortment or through the acquisition of mutations. The resulting strains have different antigenic make-ups and implicate the ability of the immune system to respond quickly following infection. Particular HLA class II allomorphs including HLA-DRB1*07:01 have been linked with the occurrence of severe influenza infections and non-response to the influenza vaccine. However, other allomorphs such as HLA-DRB1*11:01 have been shown to be protective in viral diseases such as HIV and HCV, and might be important for influenza infection. The mechanism surrounding these associations of influenza infection and HLA class II molecules expression is unclear. As some individuals expressing particular HLA allomorphs are at a greater risk of developing severe influenza infection, further investigation into the mechanism of this association is warranted. Through stimulating T cells from donors expressing HLA-DRB1*11:01 or HLA-DRB1*07:01 with an influenza epitope (HA) derived from pandemic and epidemic influenza strains, we determined the level of cross-reactivity, phenotype and polyfunctionality of the responding CD4+ specific T cells. We have compared different allomorphs and provide the first insight into the molecular basis of influenza epitope recognition by different HLA class II allomorphs, and its functional impact.
CCR4 and CCR6 Expression Characterizes Memory Tregs Subsets During HIV Infection and Correlates with Disease Progression
Authors: Salgado Gonzalo , Del Río - Estrada Perla Mariana , Avila-Ríos Santiago , Reyes-Terán Gustavo 
Published: January 2023

Abstract
Chemokine receptor expression on Tregs has been associated with pathogenesis of several diseases such as cancer, as CCR4 promotes Treg recruitment into tumors. During HIV infection, continuous Treg stimulation due to chronic inflammation has negative effects such as tissue fibrosis and limited antiviral response. We studied CCR4, CCR6, CXCR3 and CXCR5 on Treg subsets to identify homing patterns during HIV disease.
CD4+ T cells (Tc) from 33 chronic untreated (CHR) and 52 antiretroviral treated (ART) HIV donors were characterized by FACS using memory markers. Tregs were defined as CD127lowCD25hi. Analysis was performed on Cytobank and Prism 6 using non-parametric tests.
Tregs represented 7.0% and 8.0% of total CD4+ Tc in CHR and ART, respectively. Average Treg memory subsets distribution in CHR vs. ART was: Tscm=17.2% vs. 15.3%, Tcm=30.7% vs. 36.3% (p=0.0008), Ttm=27.4% vs. 25.7%. Chemokine receptor expression on total Tregs was (CHR vs. ART): R4=46.9% vs. 55.2% (p=0.0261), R6=31.6% vs. 40.1% (p=0.0043), X3=20.8% vs. 20.9% and X5=7.6% vs. 10.3%. In CHR, R4 (p=0.0007 r=0.3161) and R6 (p=0.0054 r=0.2241) frequencies correlated with CD4+ Tc count. Both markers were preferentially found on memory Treg (Tcm: R4=70.5%, R6=51.2%; Ttm: R4=93.4%, R6=65.7%) and had a significantly lower expression on non-Treg subsets (Tcm: R4=43.2%, R6=46.9%; Ttm: R4=37.0%, R6=29.9%). A similar pattern was also observed in people on ART.
We showed that Tregs are characterized by R4 and R6 expression during treated and untreated HIV infection. Both molecules are markedly found on memory phenotypes, suggesting a role in controlling homing of effector Tregs. Accumulation of R4+R6+ Tregs may reflect a response to control chronic activation that persists after ART.
Tfh Cell Metabolism and HIV-1 Infection
Authors: Syed Fahim , Yang Jing , Xia Ying , Li Wei , Yu Qigui 
Published: January 2023

Abstract
HIV-1 predominantly infects and depletes CD4 T cell populations. Multiple subsets of CD4 T cells exist, one of which is the follicular helper T (Tfh) subset. This subset is primarily present in lymphoid tissues, such as tonsil tissue, where it is specialized in helping B cells form germinal centers (GCs) for generation of high-affinity class-switched antibodies. Tfh cells in HIV-1 patients are expanded and become a major active and latent HIV-1 reservoir. To explore whether Tfh cells have a unique metabolic program that is responsible for Tfh cell expansion and survival under HIV-1 infection, we used flow cytometric analysis to sort GC Tfh (CD3+CD4+PD-1highCXCR5high) versus non-Tfh (CD3+CD4+PD-1−CXCR5−) cells from tonsil mononuclear cells for RNA sequencing (RNAseq). We found that Tfh cells express significantly lower levels of glycolytic genes, but higher levels of gluconeogenic and fatty acid oxidation genes. Inhibition of glycolysis via a lack of glucose in culture medium aided in the differentiation of Tfh cells from naive CD4 T cells and promoted Tfh cell survival against HIV-1 infection. Furthermore, use of chemical inhibition of alternative metabolic pathways effected the response of T cell subsets to HIV-1 infection. Our studies into metabolism in Tfh cells suggest a relationship between their unique metabolic phenotype and HIV-1 infection, replication and latency.
PD-1hi CD8+ tissue-resident memory T cells balance immunity and fibrotic sequelae following influenza infection
Authors: Wang Zheng , Wang Shaohua , Goplen Nick P. , Sun Jie 
Published: January 2023

Abstract
CD8+ tissue-resident memory T (TRM) cells provide frontline immunity in mucosal tissues. The mechanisms regulating CD8+ TRM maintenance, heterogeneity, and protective and pathological functions are largely elusive. Here, we identify a population of CD8+ TRM cells that is maintained by major histocompatibility complex class I (MHC-I) signaling, and CD80 and CD86 co-stimulation after acute influenza infection. These TRM cells have both “exhausted-like” phenotypes and memory features, and provide heterologous immunity against secondary infection. Using recombinant influenza virus, we demonstrate that the development of these PD-1hi “exhausted-like” TRM cells is dependent on the doses of the antigen during primary infection. Furthermore, we showed that lung CD11c+ antigen presenting cells are required for sustaining these TRM cells at the memory stage. Our data suggest that continuous antigen presentation in situ is required for the development and maintenance of these “exhausted-like” TRM cells in the lung. Strikingly, PD-L1 blockade after the resolution of primary infection promotes the rejuvenation of these “exhausted-like” TRM cells, restoring protective immunity at the cost of promoting post-infection inflammatory and fibrotic sequelae. Thus, PD-1 serves to limit the pathogenic capacity of “exhausted-like” TRM cells at the memory phase under specific tissue environment with chronic low-levels of antigen presentation following viral clearance. Our data indicate that TRM cell “exhaustion” is the result of a tissue-specific cellular adaptation that balances fibrotic sequelae with protective immunity.
Functional cytotoxic T cells exhibit tissue-specific phenotypic differences during chronic Friend virus infection
Authors: Myers Lara , Tal Michal Caspi , Messer Ronald J , Carmody Aaron B. , Weissman Irving L , Hasenkrug Kim J 
Published: January 2023

Abstract
Friend virus (FV) is a murine retroviral complex that establishes chronic infection characterized by the induction of CD4+Foxp3+ Tregs and prolonged exposure to antigenic stimulation. This leads to a state of diminished CD8+ T cell function, termed “exhaustion”, in the spleens of FV-infected mice. We report that during exhaustion there is a subset of functional CD8+ T cells defined by surface expression of signal regulatory protein alpha (SIRPα), whose expression had previously been reported on neurons, myeloid and hematopoietic stem cells but not T cells. This subset of SIRPα+ CD8+ T cells has high expression of multiple inhibitory receptors including PD-1, Tim3 and Fas, while maintaining high expression of activation/stimulatory molecules including ICOS and CD43. In addition, SIRPα+CD8+ T cells exhibit enhanced proliferation and maintain cytolytic capability, despite the conditions of exhaustion existing within the spleens of chronically infected mice. Furthermore, target cells that express the ligand for SIRPα, CD47, are more susceptible to CD8+ T cell-killing in vivo. We now demonstrate that SIRPα expression on CD8+ T cells is tissue specific, occurring in the spleen but not liver. This is interesting as we have previously reported that the liver has a 10-fold reduction of chronic FV levels, which correlates with reduced Treg-mediated suppression and increased CD8+ T cell function. Furthermore, the SIRPα− CD8+ T cells from the liver of chronically infected mice appear equivalently cytolytic to SIRPα+ CD8+ T cells from the spleen. Therefore, SIRPα expression identifies functional cytotoxic T cells in the spleen but not the liver during chronic exhaustion, highlighting tissue-specific differences of viral control.
Th1 guided evolution of protective de novo Th17 response in severe influenza
Authors: Dutta Avijit , Hung Chen-Yiu , Hsieh Yu-Chia , Chang Chia-Shiang , Chen Ting-An , Huang Yu-Lin , Lin Yung-Chang , Chen Tse-Ching , Lin Chun-Yen , Huang Ching-Tai 
Published: January 2023

Abstract
The 6.5 CD4+ T cell receptor (TCR) transgenic mice have a monotonous CD4+ TCR which responds to the hemagglutinin (HA) antigen of PR8 influenza virus. Naive 6.5 CD4+ T cells adoptively transferred into wild type mice were activated by PR8 influenza virus with Th1 response. With PR8 influenza virus infection, all CD4+ T cells in 6.5 mice were activated and they were predominantly Th1 in phenotype at the early phase of infection and Th17 at the late phase. Th1 effector responses made infected mice sick and even succumb to death. The 6.5 mice were sicker at the early phase but recovered with better survival at last. IL-17KO 6.5 mice cannot display Th17 responses and lost the survival benefit as well. IL-17 supplement at the late phase of infection enhanced survival of wild type mice with PR8 influenza virus infection. With consecutive two adoptive transfers of naive 6.5 CD4+ T cells, 6.5 CD4+ T cells of the first transfer evolved into Th1 cells but 6.5 CD4+ T cells of the second transfer demonstrated a de novoTh17 response. Thymectomy or aging in 6.5 mice limited the thymic output of naive 6.5 CD4+ T cells and diminished the Th17 response. Viral neuraminidase activated TGF-β in the Th1 6.5 CD4+ T cells at the early phase. T-bet dominance was altered with excessive ROR-γt activation in the following responding 6.5 CD4+ T cells. They have substantial IL-17 with restrained IFN-γ production. We demonstrated a Th1 guided evolution of protective Th17 response in severe influenza.
The influence of TIGIT on natural killer cell activity against HIV
Authors: Holder Kayla , Grant Michael 
Published: January 2023

Abstract
During chronic human immunodeficiency virus (HIV) infection, inhibitory molecules are upregulated and contribute to effector cell dysfunction and exhaustion. People living with (PLWH) HIV are at a greater risk for age-related morbidities, an issue magnified by human cytomegalovirus (HCMV) co-infection. As HCMV modifies NK cell phenotype and function, we considered the role of upregulated inhibitory molecules in this context and their potential to affect NK cell-based strategies to eliminate HIV-infection.
To evaluate impacts of HCMV-driven NK cell adaptation in HIV infection, PLWH were distinguished by HCMV status or by high (&gt;20%) versus low (&lt;6%) percentages of adapted NK cells. Adapted NK cells did not display a classical exhausted phenotype as there was low LAG-3, PD-1 (&lt;1%), and TIM-3 (&lt;10%) expression. In contrast, TIGIT was present on a large fraction of NK and CD8pos T cells and levels were associated with HCMV status. Since CD4pos T cells latently infected with HIV upregulate CD155, a ligand for TIGIT, we investigated TIGIT modulation of NK cell functions. Blocking TIGIT/CD155 interactions increased NK cell cytotoxicity and correlated with the extent of NK cell adaptation to HCMV. Engaging TIGIT reduced levels of antibody-dependent cell-mediated cytotoxicity (ADCC) against pseudo HIV-infected (vPE16) P815 cells with the extent of reduction again reflecting NK cell adaptation to HCMV. Measuring HIV-specific ADCC against HIV-infected CEM.NKR CCR5pos cells transduced with CD155 will allow assessment of the role of TIGIT inhibition in a genuine HIV infection model. Blocking TIGIT may be an appropriate strategy to invigorate antibody-dependent NK cell activity against HIV reservoirs in cure or treatment strategies.
CD8 regulatory T cells during Zika virus infection
Authors: Zanluqui Nagela Ghabdan , de Oliveira Lilian Gomes , Polonio Carolina Manganeli , de Oliveira Marilia Garcia , de Souza Angelo Yan , Peron Jean Pierre Schatzmann 
Published: January 2023

Abstract

Introduction
Flavivirus infections are cause of great concern worldwide due to recurrent epidemics and high mortality rates, being a major public health problem. The relevance to study Zika virus infection was highlighted after the discovery that ZIKV infection during pregnancy could cause microcephaly, besides others abnormalities. Knowing that ZIKV, like other flaviviruses, can modulate host innate and adaptive immune response, we aim to understand the role of CD8+ regulatory T cells in the control of viral replication in an experimental infection.

Methods
C57BL/6 Foxp3GFP and C57BL/6 CD8−/− mice were infected with 106 PFU of ZIKV (Brazilian strain), followed by viral quantification, gene expression, and flow cytometry analysis.

Results
Infection of CD8 knockout mice presented viral load with an oscillatory profile compared to WT mice, and analysis of CD8 T cells populations in WT mice showed that CD8Foxp3 cells are induced on the first day post infection and it pool of cells are maintained during infection, as could be noted on day 30 post infection. These cells are related to increase of viral replication as shown in cell transfer experiment. However, naïve CD8Foxp3 cells are responsible to increase virus replication, while CD8Foxp3 cells from infected mice seems to be not capable to respond to antigen.

Conclusion
This finding leads us to believe that there is an attempt by the pathogen to modulate the adaptive immune response, in order to facilitate its replication and permanence in the host. In short, our work seeks to elucidate the immunobiology of the ZIKV infection and to correlate this with the susceptibility to the Congenital Syndrome caused by Zika virus.