bluuebunny/crossref_metadata_2025_split huggingface dataset:
Memory immune mechanisms against parasitic tissue-dwelling Heligmosomoides polygyrus larvae (133.25)
Authors: Kreider Timothy , Gaydo Andrew G , Urban, Jr. Joseph F , Gause William C 
Published: January 2023

Abstract
The nematode parasite H. polygyrus has both a parasitic intestinal tissue-dwelling larval phase and a lumen-dwelling adult phase in its life cycle. Primary inoculation of naïve mice resulted in chronic infection while secondary inoculation after drug-cure to clear adult worms triggered a protective Th2-type memory response, characterized by a distinct Th2-type granuloma that developed by 4 days after secondary but not primary inoculation. We investigated the effects of this memory response on early larval development. As early as day 4 after inoculation, parasitic larvae in the intestine were fewer in number, exhibited shorter lengths, and were more widely distributed across the small intestine in the memory compared to the primary response. Mice administered DMFO, which inhibits ornithine decarboxylase, after secondary inoculation exhibited significantly increased larval numbers and lengths, but no change in parasite distribution, suggesting an important role for polyamines in sustaining a host-protective memory response. In addition, B cell-deficient mice contained larvae with increased lengths and altered distribution in the intestine after secondary inoculation that was comparable to the response observed after a primary inoculation. The early host-protective response appeared to be TSLP-independent because it was not impaired in TSLPR-/- mice. These studies suggested that memory Th2-type responses impaired tissue-dwelling parasite migration and development as early as four days after infection, and that this response was partly dependent on polyamine production and B cells.
Macrophages are significant producers of IL-1beta during C. muridarum genital tract infection and IL-1beta secretion is dependent on chlamydial viability but not growth (133.3)
Authors: Prantner Daniel , Brade Helmut , Rank Roger , Nagarajan Uma 
Published: January 2023

Abstract
Recent findings have implicated secretion of the proinflammatory cytokine interleukin-1β as a crucial player in female genital tract pathology during chlamydial infection. However, the major cellular source of IL-1β during an in vivo infection and mechanistic details of its release have yet to be determined. In the present study, flow cytometry was used to isolate highly enriched cell populations from the genital tracts of C. muridarum infected mice at the peak of IL-1β secretion. Purified F4/80+ macrophages and Ly-6G+ neutrophils, but not CD45- epithelial cells, expressed high levels of both IL-1β mRNA and protein. Macrophages infected with C. muridarum in vitro secrete low amounts of IL-1β, however they can be induced to secrete high amounts when prestimulated with E. coli LPS prior to infection. Prestimulation with purified LPS from C trachomatis L2 was also sufficient to amplify IL-1β secretion, suggesting that prestimulation by chlamydial ligands could account for the high levels of IL-1β observed in vivo. Using LPS prestimulated macrophages as a model system, it was further determined that IL-1β secretion was dependent on activation of the protease caspase-1 in a manner that required both potassium efflux and the activity of serine proteases. Additionally, chlamydial-induced IL-1β secretion was blocked when chlamydiae were inactivated by UV irradiation or heat treatment but occurred normally during treatment with chloramphenicol, rifampin, and INP0007, illustrating that only bacterial viability and not bacterial growth is necessary for this response. This study was supported by NIH grant #AI067678.
SLAM controls killing of bacteria through regulation of phosphatidylinositol-3-phosphate in phagosomes (133.31)
Authors: Berger Scott B , Romero Xavier , Wang Ninghai , Faubion William A , Terhorst Cox P 
Published: January 2023

Abstract
Macrophages eradicate pathogens by phagosomal reactive oxygen species, nitric oxide and by exposure to phagolysosomal enzymes. Whereas a number of surface receptors are requisite for recognition and entry of bacteria into the phagosome, their role in bacterial killing is largely unknown. Here we show that the surface receptor SLAM (Slamf1, Cd150) enters the macrophage phagosome together with Gram-negative, but not with Gram-positive bacteria. In the bacterial phagosome, SLAM regulates production of phosphatidylinositol-3-phosphate (PI3P), which is a key factor in the assembly of the active NADPH-oxidase (Nox2) enzyme complex, as well as in phagosome maturation. Consequently, these two bactericidal processes are defective in the absence of SLAM, resulting in an impaired clearance of attenuated S. typhimurium sseB- in SLAM-deficient mice. This is the first example of a surface receptor, which is a co-stimulatory molecule in T cell responses, also governing distinct functions in intracellular vesicles of phagocytic cells.
This work was supported by a grant from the NIH (AI-15066)
Role of galectin-3 in macrophage response to Listeria monocytogenes infection (133.34)
Authors: Weng I-Chun , Hsu Daniel K , Liu Fu-Tong 
Published: January 2023

Abstract
Galectin-3 is a β-galactoside-binding animal lectin expressed in various immune cell types including macrophages. It has been implicated as a positive regulator of macrophage phagocytosis and as a negative regulator of LPS-mediated inflammation. However, its role in macrophage antibacterial function has not been fully elucidated. The aim of this study was to investigate the role of galectin-3 in macrophage antibacterial function against Listeria monocytogenes (LM) infection by studying bone marrow-derived macrophages (BMM) from galectin-3-deficient (gal3-/-) and wild-type (gal3+/+) mice. After in vitro infection, gal3-/- BMM contained significantly fewer viable intracellular bacteria than gal3+/+ BMM. Consistently, immunofluorescent staining of infected BMM revealed a significantly lower percentage of cytosolic LM escaped from phagosomes in gal3-/- BMM compared to gal3+/+ BMM. Higher levels of reactive nitrogen intermediate nitric oxide (NO) but lower levels of inflammatory cytokine IL-1β were detected in LM-infected gal3-/- BMM compared to gal3+/+ cells. In addition, we noted elevated levels of NAD(P)H in gal3-/- BMM which may contribute to higher amounts of NO in gal3-/- BMM. We conclude that galectin-3 plays a regulatory role in macrophage antibacterial function by interfering with the production of NO, thereby facilitating the survival and replication of intracellular bacteria.
Rapid deletion of antigen-specific CD4+ T cells following infection represents a strategy of immune evasion and persistence for Anaplasma marginale (133.36)
Authors: Han Sushan , Norimine Junzo , Wendy Brown C. 
Published: January 2023

Abstract
We reported the rapid and permanent deletion of immunization-induced bovine CD4 T cell responses to Anaplasma marginale major surface proteins (MSPs) after infection. To determine if antigen-specific T cells were anergic, sequestered, or deleted, CD4 T cells specific for a MSP1a T cell epitope were enumerated with a DRB3*1101 tetramer. The pre-challenge frequency of tetramer+ CD4+ cells of 0.025% dropped rapidly at the peak of infection to control levels of 0.0003%, paralleling loss of antigen specific T cell responses. Background frequencies of tetramer+ CD4+ T cells in spleen and lymph node indicated lack of sequestration. We hypothesize that this rapid and long-term deletion of specific T cells is driven by high antigen load during acute and persistent infection. To test this, cattle immunized with MSP1a and MSP2 of A. marginale will be challenged with A. marginale or A. centrale, a subspecies in which MSP2 but not MSP1a epitopes are conserved with those in A. marginale. We predict deletion of CD4+ T cells specific for MSP1a and MSP2 after infection with A. marginale, but only deletion of MSP2-specific T cells after infection with A. centrale, as MSP1a-specific T cells will not be exposed to high antigen load in the latter cattle. This experiment will determine if infection-mediated CD4+ T cell depletion is dependent on the presence of specific antigen in the infecting pathogen.
ATP plays a role as a danger signal that activates macrophages during adenoviral infection (133.38)
Authors: Lee Benjamin H , Kushwah Rahul , Bertics Paul , Hu Jim 
Published: January 2023

Abstract
We have previously shown that adenovirus infection of epithelial cells and macrophages co-culture resulted in synergistic induction of pro-inflammatory mediators such as cytokines, nitric oxide (NO), and reactive oxygen species (ROS) and caused cytotoxic responses. Here, we investigated whether ATP plays a role during the inflammatory response against adenovirus using the co-culture system. We found that pre-treatment of the co-culture with oxidized-ATP inhibited induction of NO and ROS and reduced cytotoxicity during adenoviral infection. Furthermore, we demonstrated that ATP signalling through P2X7 receptor is required in generation of NO and ROS using P2X7 deficient macrophage cell line. These results indicate that ATP plays a role as a danger signal to regulate macrophage activation during inflammatory response against adenoviral infection.
Reawakening Retrocyclins: Ancestral Human Defensins Active Against HIV-1 (133.49)
Authors: Cole Alexander M , Venkataraman Nitya , Ruchala Piotr , Waring Alan J , Lehrer Robert I , Stuchlik Olga , Pohl Jan 
Published: January 2023

Abstract
Human alpha and beta defensins contribute substantially to innate immune defenses against microbial and viral infections. Certain nonhuman primates also produce theta-defensins - 18 residue cyclic peptides that act as HIV-1 entry inhibitors. Multiple human theta-defensin genes exist, but they harbor a premature stop codon that blocks translation. Consequently, the theta-defensins (retrocyclins) encoded within the human genome are not expressed as peptides. In vivo production of theta-defensins in rhesus macaques involves the post-translational ligation of two nonapeptides. Neither the mechanism of this unique process nor its existence in human cells is known. To ascertain if human cells retained the ability to process demidefensins, we transfected human promyelocytic cells with plasmids containing repaired retrocyclin-like genes. The expected peptides were isolated, their sequences were verified by mass spectrometric analyses, and their anti-HIV-1 activity was confirmed in vitro. Our study reveals for the first time that human cells have the ability to make cyclic theta-defensins. Given this evidence that human cells could make theta-defensins, we attempted to restore endogenous expression of retrocyclin peptides. Since human theta-defensin genes are transcribed, we used aminoglycosides to read-through the premature stop codon found in the mRNA transcripts. This treatment induced the production of intact, bioactive retrocyclin-1 peptide by human epithelial cells and cervicovaginal tissues. Since retrocyclins are broadly antiviral, the ability to reawaken retrocyclin genes from their 7 million years of slumber could provide a novel way to secure enhanced resistance to several major viral pathogens. AI052017; AI065430
Predictors of human norovirus infection and immunity (133.52)
Authors: Leon Juan S , Fernandez Marina L , Ailes Elizabeth C , Lindesmith Lisa C , Seitz Scot R , Smith Emily R , Baric Ralph S , Moe Christine L 
Published: January 2023

Abstract
Noroviruses (NoV) are the main cause of epidemic gastroenteritis worldwide. We have previously shown that both an individual's secretor status (genetic) and induction of Norwalk virus-specific salivary IgA (immune) are important predictors of infection with Norwalk virus (NV). We still do not understand the factors that mediate the immune response, and infection, to Norwalk virus. To address this need, we have extended our analysis of immunological, genetic, and demographic parameters of 109 volunteers challenged with various doses of Norwalk virus through univariate and multivariate regression analyses. We found that gender, ethnicity, levels of pre-challenge NV-specific serum IgG or levels of pre-challenge NV-specific salivary IgA were not significant predictors of infection or development of a NV-specific antibody response. The presence but not magnitude of pre-challenge serum NV-specific IgG and secretor positive status were significantly associated with infection. Dose of inoculum received and age of the individual may also be predictors of infection and development of an NV-specific antibody response. We observed significant collinearity between the age of the volunteer and the presence of pre-challenge serum NV-specific IgG. Lastly, we found a strong association between levels of salivary and serum NV-specific antibody levels, after adjusting for covariates. Taken together, these data will be used to better understand the immune response to NV infection and design effective NoV vaccines to protect at risk populations including children, food handlers, and the elderly.
B and T lymphocyte attenuator tempers early infection immunity (133.6)
Authors: Brown Nicholas K. , Sun Yonglian , Miller Mendy , Fu Yang-Xin 
Published: January 2023

Abstract
Co-inhibitory pathways are thought to act in later stages of an adaptive immune response, but whether co-inhibition contributes to early innate immunity is unclear. We show that engagement of the newly discovered co-inhibitory receptor B and T lymphocyte attenuator (BTLA) by herpesvirus entry mediator (HVEM) is critical for negatively regulating early host immunity against intracellular bacteria. Both HVEM-/- and BTLA-/-, but not LIGHT-/-, mice are more resistant to listeriosis compared to wild type mice, and blockade of the BTLA pathway promotes, while engagement inhibits, early bacterial clearance. Differences in bacterial clearance were seen as early as 1 day post-infection, implicating the initial innate response. Therefore, innate cell function in BTLA-/- mice was studied. We show that innate cells from BTLA-/- mice have a lower threshold for activation, and secrete significantly more pro-inflammatory cytokines upon stimulation with listeria. These results provide the first evidence that a co-inhibitory pathway plays a critical role in regulating early host immunity against infection. (Supported by CA115540, AI062026, and DK58897 to YXF and T32AI007090 to NKB)
Decreased IL-15 Production and Impaired Natural Killer Cell Activity in Influenza Infected C57BL/6 Aged Mice (133.9)
Authors: Nogusa Shoko , Ritz Barry W , Gardner Elizabeth M 
Published: January 2023

Abstract
The role of Natural Killer (NK) cells during the innate immune response to primary influenza infection was investigated in young and aged mice. Young (2~6mon) and aged (22mon) C57BL/6 mice were infected intranasally with influenza A (H1N1, PR8) and NK cell cytotoxicity was assessed in lung and spleen during the first 3 days of infection. Aged mice demonstrated both decreased influenza-inducible NK cytotoxicity and reduced percent and number of NK cells relative to young mice. To establish a role of NK cells in controlling influenza infection, NK cells were depleted in young mice by injecting anti-NK1.1 antibody prior to infection. NK-depleted young mice exhibited increased weight loss and elevated lung virus titers compared to intact young or aged mice. These data indicate that NK cell function is impaired in aged mice, and more importantly, indicate the essential role of NK cells in controlling virus titers in lung, regardless of age. Notably, NK cells from young and aged mice had similar lytic efficiencies. However, aged mice demonstrated reduced plasma IL-15 levels relative to young mice. These results suggest that the NK cell residing environment is compromised in aged mice and, that decreased IL-15 in aged mice may be associated with decreased NK cell proliferation or survival, resulting in decreased NK cell number and an impaired total NK cell response to influenza infection. Supported by NIH AG029637-01.
Auto-antigenic stimulation potentiates NKT cells for subsequent innate IFN-gamma secretion (134.23)
Authors: Wang Xiaohua , Gumperz Jenny 
Published: January 2023

Abstract
NKT cells produce protective immune mediators at early stages of infections, preceding the responses of MHC-restricted T cells, and thus are thought a key bridge between innate and adaptive immune responses. Early IFNγ secretion by NKT cells during bacterial infections can result from autoantigenic activation with co-stimulation from IL-12&IL-18. However, the cellular processes underlying the rapid responsiveness of NKT cells remain poorly understood. Here we show that auto-antigenic stimulation of NKT cells potentiates them to secrete IFNγ in response to subsequent exposure to IL-12&IL-18. Rested NKT cells did not respond to IL-12&IL-18, however, NKT cells pre-exposed to CD1d+ APCs subsequently showed a transient ability to transcribe IFNγ mRNA and to secrete IFNγ protein in response to these cytokines without concurrent TCR stimulation. The potentiation effect was dependent on TCR signaling during pre-exposure. The subsequent cytokine response was p38 dependent and calcium signaling independent. The potentiation effect was transient, which distinguishes it from classical Th1 differentiation. The window of responsiveness was not due to regulation of cytokine receptor expression on NKT cells. Thus, we hypothesize that autoantigenic activation may induce epi-genetic changes in NKT cells that transiently confer an innate-like ability to respond to cytokines without concurrent TCR signaling.
Role of CCL2-producing PMN on the conversion of naive monocytes to M2bMonocytes (134.28)
Authors: Asai Akira , Shigematsu Kenji , Kobayashi Makiko , Herndon David N , Suzuki Fujio 
Published: January 2023

Abstract
CCL1-producing monocytes with immunosuppressive properties (M2bMonocytes) have been demonstrated in peripheral blood of severely burned patients. Also, these burned patients are shown to be carriers of CCL2-producing PMN (PMN-II). Neither M2bMonocytes or PMN-II has been demonstrated in peripheral blood of healthy donors. In this study, the role of PMN-II on the conversion of naive monocytes to M2bMonocytes was investigated. PMN-II were induced from immuature PMN after stimulation with 0.0075% SAC and 10-6 M terubutaline. Immature PMN were obtained from peripheral blood of healthy volunteers 3 hrs after 1-hr of programmed exercise, as previously described. PMN-II (upper chamber) were transwell-cultured with naive monocytes (syngeneic to PMN-II, lower chamber) for 24 hrs. Cells harvested from the lower chamber were re-cultured for 24 hrs for the production of CCL1 (a biomarker of M2bMonocytes), and culture fluids obtained were assayed for CCL1 by ELISA. Naive monocytes did not produce CCL1 even when they were transwell-cultured with healthy donor PMN (normal PMN). However, CCL1 was detected in culture fluids of naive monocytes that were previously cultured with PMN-II. Anti-CCL2 mAb inhibited the appearance of M2bMonocytes in transwell-cultures between naive monocytes and PMN-II. Also, M2bMonocytes were generated from naive monocytes after they were cultured with recombinant CCL2. These results indicate that PMN-II, or CCL2 produced by PMN-II, play an important role on the generation of M2bMonocytes commonly demonstrated in burn patient peripheral blood. This study was supported by SHC NA #8840.
IL-17-induced apoptosis correlates positively with the release of myeloperoxidase in isolated neutrophils from mice (134.32)
Authors: Silverpil Elin , Glader Pernilla , Lindén Anders 
Published: January 2023

Abstract
BACKGROUND
Interleukin (IL)-17 can recruit neutrophils (PMNs) through indirect mechanisms and thereby contribute to pulmonary host defense. IL-17 may induce PMN apoptosis as well; and this through a direct mechanism (Silverpil et al, EAACI 2007). We now determined whether IL-17-induced PMN apoptosis is associated with increased bactericidal activity.
METHODS
Blood PMNs from Balb/c mice were isolated and cultured in vitro (48 hrs) in medium with mouse recombinant IL-17 protein (1-100 ng/mL) or in medium alone (control). Apoptosis and necrosis of the PMNs were measured on a flow cytometer targeting Annexin V and 7AAD, whereas the bactericidal activity was assessed by measuring extracellular myeloperoxidase (MPO) in the conditioned medium using ELISA. Data shown as (mean [SEM]), n=4-6.
RESULT
IL-17 increased PMN apoptosis (Annexin V+, 7AAD-) from 34 [1] % in the control group to a maximum of 55 [8] % (p&lt; 0.05, Mann-Whitney U-test), but it did not affect PMN necrosis (Annexin V+, 7AAD+, not shown). The MPO concentration correlated positively with PMN apoptosis (p&lt;0.01, Spearman's rank correlation).
CONCLUSION
This study demonstrates that IL-17-induced PMN apoptosis correlates with MPO release in vitro. This finding suggests that IL-17 is involved in terminating the innate component of pulmonary host defense in a controlled manner, while at the same time maintaining bactericidal activity.
Macrophages express a TCRαβ-based variable immunoreceptor (134.34)
Authors: Puellmann Kerstin , Beham Alexander W , Fuchs Tina , Kzhyshkowska Julia , Gratchev Alexei , Laird Rebecca , Wessels Johannes T , Neumaier Michael , Ganser Arnold , Kaminski Wolfgang E 
Published: January 2023

Abstract
Immunological dogma holds that variable immunoreceptors are restricted to lymphocytes. However, recent studies demonstrate that a subpopuation of human neutrophils expresses the TCRαβ (PNAS 103:14441, 2006) and mouse thymic granulocytes exhibit rearrangement of their TCR loci (Nature 452:764, 2008). Here, we provide evidence that a subpopulation of circulating human monocytes, monocyte-derived macrophages and tissue macrophages constitutively express a TCRαβ-based variable immunoreceptor.
TCRαβ + monocyte/macrophage subpopulations were assessed using with laser scanning cytometry and repertoire diversities were determined by CDR3 spectratyping. We find that human macrophages express individual-specific TCR Vαβ repertoires. Th1 or Th2 cytokine dependent in vitro differentiation triggers expression of distinct Vαβ repertoires in macrophages. Moreover, Th1 polarized macrophages show enhanced secretion of the major monocyte chemoattractant MCP-1 in response to costimulation with αCD3/CD28 .
The presence of a variable immunoreceptor in macrophages together with our previous identification of the TCR in a subset of neutrophils challenge the traditional dichotomy of the vertebrate immune system into non-specific/myeloid and antigen-specific/lymphoid immunity. They unravel a much closer kinship between both lineages than commonly assumed.
Supported by DFG grants KA 1078/4-1, BE 1768/5-1