bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antibody can mediate protective immunity at early tissue-dwelling stages of intestinal helminth infection (37.27)
Authors: Bowdridge Scott , Liu Qian , Kreider Timothy , Liu Zhugong , Song Youngmia , Gaydo Andrew , Urban Joseph , Gause William 
Published: January 2023

Abstract
B cells may be critical in mediating protective immunity by aiding Th2 cell development and/or antibody production. To examine the role of B cells during helminth infection B cell-deficient mice were inoculated with one of two intestinal nematode parasites: Nippostrongylus brasiliensis (Nb) and Heligmosomoides polygyrus (Hp). A similar pattern in elevation of Th2 cytokine gene expression was seen in B cell-deficient and WT mice after inoculation with either species. No difference in worm expulsion was found between B cell-deficient and WT mice after Nb infection, but differences in worm expulsion occurred after Hp inoculation. At day 4 and day 7 after secondary Hp challenge impaired larval migration and development occurred in WT but not B cell-deficient mice suggesting that both early invasion and in situ larval development were inhibited through B cell-dependent mechanisms. Administration of immune serum to B cell-deficient mice restored protective immunity and when given to naïve mice mediated protective effects, suggesting a primary role for antibody in protective immunity during Hp infection. Thus, these data indicate that B cells contribute to protective immunity during Th2-types responses primarily through their production of antibodies and that their importance varies among different species of intestinal helminthes.
Distinct signaling pathways during innate and adaptive immune responses to Aspergillus fumigatus induce alternatively activated macrophages expressing Th2 cytokines (37.37)
Authors: Bhatia Shikha , Fei Mingjian , Oriss Timothy , Yarlagadda Manohar , Rooijen Nico , Ray Anuradha , Ray Prabir 
Published: January 2023

Abstract
Macrophages adopt an ‘alternative phenotype’ in a Th2-mediated inflammatory environment. Although identified in a wide variety of disease conditions, alternatively activated macrophages (AAMs) have been functionally best studied in helminth infections. The heterogeneity of functions performed by AAMs is attributed to the diverse molecules they express. Since infection with the fungus, Aspergillus fumigatus induces a chronic allergic response in patients with cystic fibrosis and asthma, we investigated the participation of AAMs in the process. We have found that Aspergillus infection promotes early recruitment of AAMs to the lung and the cells possess features of both AAMs and Th2 cells. The AAMs produce Th2 cytokines, which is independent of Dectin-1 signaling. Interestingly, unlike in helminth infections, both AAM recruitment and Th2 cytokine production were found to be independent of IL-4Rα and STAT6. Besides being part of the innate immune response to A.fumigatus, AAMs were also induced during adaptive immune response to the fungus. However, at this later time, AAM recruitment and their typical features were abolished in the absence of IL-4Rα and STAT6. Collectively, our studies show that different signaling pathways regulate the development of AAMs in the innate and adaptive arms of the immune response to A. fumigatus. Being early producers of Th2 cytokines, the presence of AAMs would be deleterious to the host unless regulated efficiently.
RSV-induced polarization of lung DCs towards plasmacytoid DCs with an associated Th2 response is dependent on NKT cells in the neonatal lungs (37.46)
Authors: Habeeb Keith , Durre Kainath , Sun Jonathan , Qureshi Mahboob 
Published: January 2023

Abstract
RSV bronchiolitis and pneumonia during early infancy is associated with increased susceptibility to asthma; and is characterized by a hyper-responsiveness airway and a predominant Th2 response. Using a BALB/C neonatal mouse model we have observed a skewed polarization of DCs towards plasmacytoid DCs (pDCs: CD11blo CD11clo CD45R+) over myeloid DC (mDCs: CD11blo CD11chi/med CD45R-), as determined by flow cytometry (FACS). This was associated with increased and decreased production of Th2 (IL-10) and Th1 (IFN-g) cytokines, respectively, in the alveolar spaces, as measured by ELISA. A temporal observation of enhanced NKT (CD3-CD19-CD1d+) cell response was also determined by FACS. In addition, FACS revealed that RSV infection of NKT cell knock out (CD1d-/-) neonatal mouse had lower proportions of pDCs and a higher proportions of mDCs compared to the wild type (WT) mouse of same age. Amount of IL-10 in bronchoalveolar lavage fluid was lower in the CD1d-/- mouse than that in the WT mouse. This data suggests that NKT cells are instrumental in skewed polarization of DC in response to RSV infection, which in turn may influence the T cell responses and hence, development of susceptibility to asthma in later life.
Distinct migratory behavior of myelomonocytic cells and antigen specific CD8 T cells during infections with Listeria monocytogenes (37.48)
Authors: Williams Cassandra , Velázquez Peter , Dustin Michael 
Published: January 2023

Abstract
Listeria Monocytogenes is a facultative, gram-positive, intra-cytosolic pathogen that causes severe infections in immunocompromised individuals. Listeria infections are characterized by the formation of leukocyte rich infectious foci in the liver and spleen. In order to establish the spatiotemporal interactions that must occur between innate and adaptive immune cells during the formation of infectious foci in the liver, intravital microscopy was employed. The quantitative analysis of acute changes in LysM+ neutrophil migration in response to Listeria challenge showed an increase in directed migration and direct contacts made with Listeria positive Kupffer cells. Additionally, Listeria foci filled with LysM+ granulocytes exclude blood, indicating that both a physical barrier and hypoxia may facilitate bacterial resistance. Upon adoptive transfer of Listeria specific CD8+ T cells it was found that T cell receptor specificity did not affect patrolling of effector CD8+ T cells near foci. This suggests that non-specific adhesion mechanisms are dominant players in lymphocyte behavior near foci. Together, these data provide insight into the spatiotemporal interactions that direct leukocyte behavior and the physical mechanisms underlying protection from Listeriosis.
RELM-beta is required for optimal development of theTh2 cytokine response to the intestinal parasite Heligmosomoides polygyrus (37.53)
Authors: Patel Nirav , Mishra Pankaj , Gause William 
Published: January 2023

Abstract
Previous studies have suggested that resistin-like molecule beta (RELM-beta) contributes to protective immunity against intestinal nematode parasites by directly interfering with adult worm feeding in the lumen. Other studies have suggested that RELM-beta may also function in the mucosal milieu by regulating Th1/Th2 cytokine production. In our studies, we examined the development of the memory Th2-type response to the murine intestinal nematode parasite, Heligmosomoides polygyrus (Hp). Mice were inoculated with Hp, drug-cleared at day 14, and several weeks later given an Hp secondary inoculation. Consistent with previous studies, adult worm burden was increased in Hp inoculated RELM-beta KO compared to inoculated WT controls. Analysis of cytokine gene (RT-PCR) and protein (ELISPOT) expression in draining mesenteric lymph nodes (MLNs) showed reductions in Th2 cytokine levels in RELM-beta KO compared to WT mice at day 7 after Hp secondary inoculation. At this time point spleen weight and total numbers of MLN CD4+ T cells and B cells were also reduced in RELM-beta KO compared to WT mice. Analysis of sorted CD4+ T cells showed reduced IL-4 expression in RELM-beta KO mice compared to WT mice at day 7 after secondary inoculation. These studies suggest that RELM-beta may affect protective immunity through multiple mechanisms, including enhancement of theTh2 cytokine response.
A strategy to identify human monoclonal antibodies that neutralize a broad spectrum of influenza A subtypes (38.12)
Authors: Olsen Ole , Frey Steve , Boozer Christy , Grandea Glen , Cicarelli Mike , Lily Rebecca , Ward Courtney , Fitch Alison , Feng I-wei , Jellyman David , Grondin Roxanne , Gibbs Aaron , Chan-hui Po-ying , Whitman Darbie , Fox Ray , Mosley Bruce , Hammond Phil , Branum Mark , Cieplak Witold , Moyle Matthew 
Published: January 2023

Abstract
Influenza A continues to be a serious public health threat as it continuously evolves to evade and escape immune surveillance through genetic drift, shift, and re-assortment. Hemagglutinin (HA) is the main glycoprotein target of the humoral immune response and elicits protective, neutralizing, antibodies during infection. However, these antibodies are usually specific for the influenza subtype causing infection and exhibit a narrow spectrum of protectiveness. To date, many of the influenza-neutralizing monoclonal antibodies described are cross-specific for subtypes H1 and H5 but do not neutralize subtypes H3 or H7. Therefore, we have designed an approach to survey the human B cell repertoire to identify monoclonal antibodies that neutralize influenza viruses of both the H1 and H3 subtypes. Our strategy is to identify humans that have broadly reactive serum antibodies, culture IgG+ memory B cells from these individuals at near clonal density, and then assay the culture supernatants for the presence of antibodies that neutralize both H1 and H3 influenza subtypes. By combining functional and binding assays we will determine if there exist in nature highly conserved neutralizing epitopes that are represented on most or all of the influenza HA subtypes tested.
Viral induced T cell independent B cell activation (38.13)
Authors: Blutt Sarah , Conner Margaret 
Published: January 2023

Abstract
Many acute viral infections induce early T cell independent polyclonal B cell activation and production of antigen-specific antibody prior to the formation of classical germinal centers. Rotavirus, a well characterized intestinal virus, induces Peyer’s patch (PP) T cell independent B cell activation and viral-specific IgA production in mice within 48 hours after viral exposure. We have utilized an in vitro culture system to identify important factors required for viral-induced B cell activation. We found that CD11c+ dendritic cells were essential for viral-induced B cell activation and that conditioned medium from virus-treated dendritic cells was sufficient to induce B cell activation indicating that direct contract between the dendritic cell and B cell is not required. PP dendritic cells contained rotavirus antigen and were activated during viral infection in vivo, concurrent with B cell activation, suggesting that dendritic cells are important modulators of the B cell response to rotavirus in vivo as well as in vitro. Our findings suggest that dendritic cells modulate the production of rapid T cell independent pathogen-specific antibody in the PP. Defining how pathogens induce rapid but specific antibody has tremendous potential to define the role of early antibody in limiting viral replication and dissemination and providing protection.
Regaining of the functions of antibodies in HIV-1-infected individuals (38.2)
Authors: Yu Qigui , Hu Weiguo , Hu Ningjie , Byrd Daniel , Amet Tohti , Qin Xuebin 
Published: January 2023

Abstract
Patients infected with HIV-1 are well known to mount a vigorous and sustained antibody (Ab) response to the virus. This response is also well known to have a limited effect on controlling virus proliferation or on protecting the patients from developing AIDS. This puzzling and frustrating phenomenon has been explained as the consequence of the incorporation and hijacking of regulators of complement activation (RCA) on HIV-1 virions and infected cells, which blocks Ab-dependent complement-mediated lysis (ADCML) of HIV-1 virions and infected cells by inhibiting the formation of the membrane attack complex (MAC) at the terminal stage of the complement activation cascades. Here, we report a potent and specific inhibitor of human CD59 (hCD59), one major member of human RCA. This inhibitor (designated rILYd4) was developed as a recombinant protein (114 aa) from the fourth domain of the bacterial toxin intermedilysin. We showed that rILYd4 in conjunction with polyclonal Abs to HIV-1 envelope, or with sera from HIV-1-infected patients at different stages of viral infection, efficiently abrogated hCD59 function and rendered complement-resistant HIV-1 virions including lab strains and primary isolates sensitive to ADCML. Toxicity assay using erythrocytes suggested rILYd4 has no or minimal non-specific cytotoxic effect. These results indicate that rILYd4 may represent a novel therapeutic agent for regaining the functions of Abs in HIV-1-infected patients to combat HIV-1 infection.
The kinetics of B-cell trafficking and long-term maintenance in the CNS induced by Sindbis virus infection (39.14)
Authors: Metcalf Talibah , Griffin Diane 
Published: January 2023

Abstract
Anti-viral antibodies are essential for both the clearance of Sindbis virus (SINV) and long-term suppression of reactivation in the CNS. To characterize the changing functional characteristics of B-cells and identify important determinants of B-cell trafficking and long-term maintenance, CNS tissue from SINV-infected mice was assessed at various times post-infection (pi) using flow cytometry and qRT-PCR. Plasmablasts (PBs) and memory B-cells (MBs) (CD19+CD38+CD138-IgM-IgD-) were 70% of the B-cell population for at least 6-mo pi, while plasma cells (CD19+/-CD38-CD138-) were less than 5% of the population. Staining for intracellular and surface IgG at day 26 pi detected 50% PBs and 60% MBs. A small population of CD19+CD38-CD138- cells was detected indicating possible germinal center (GC) B-cells in the brain. Further staining for GC marker GL-7 detected GL-7+ CD38+/- cells in the brain for at least 1-mo pi. mRNA levels of CXCL9/CXCL10 (trafficking), CCL19/CXCL13 (follicle formation), and BAFF (B-cell survival) peaked on days 5-7 pi. Levels gradually decreased and returned close to baseline by 6-mo pi except for BAFF that was maintained at a low level. The expression of CXCR3, CCR7, and BAFF receptor were detected on B-cells for at least 1-mo pi. These results suggest that PBs and MBs play a role in the long-term suppression of SINV replication and that the brain may provide a microenvironment for differentiation and survival of B-cells.
T-cell receptor repertoire diversity during persistent and fatal ehrlichial infections (40.17)
Authors: Thirumalapura Nagaraja , Thomas Sunil , Soong Lynn , Walker David 
Published: January 2023

Abstract
Human monocytotropic ehrlichiosis (HME), an emerging tick-transmitted bacterial disease, is caused by Ehrlichia chaffeensis. HME is modeled in C57BL/6 mice using Ehrlichia muris, which causes persistent infection, and Ixodes ovatus Ehrlichia (IOE), which is either acutely lethal or sub-lethal depending on the dose and route of inoculation. To better define the roles of T cells in protection and pathogenesis, we analyzed TCR Vβ usage in activated T cells from mice infected with E. muris or IOE by TCR-CDR3 spectratyping. Our data indicated that E. muris, but not IOE, induced oligoclonal expansion of CD4+ T cells within the several Vβ families (Vβ1, Vβ2, Vβ8.1, Vβ8.2, Vβ12, Vβ16 and Vβ19) early during the effector phase of T cell response. Further, oligoclonal expansion of CD8+ T cells within the Vβ8.2, Vβ4 and Vβ19 families was observed during E. muris infection compared to oligoclonal expansion of Vβ16 and Vβ19 CD8+ T cells in mice infected with IOE. Functional analysis of T cell subsets by flow cytometry indicated that E. muris induced a strong Th1 response involving several Vβ families compared to a weak Th1 response induced by IOE. The data suggested that unlike IOE, E. muris induces a strong Th1 response which tends to focus on certain Vβ families early during the effector phase of T cell response. Future studies will focus on functional characterization of memory T cell subsets induced following infection with E. muris.
Using team-based learning (TBL) to teach immunology to biomedical science graduate students (41.2)
Authors: McCormack Wayne , Garvan Cynthia 
Published: January 2023

Abstract
Purpose: The focus of team-based learning (TBL) on problem-solving and integration of information has tremendous potential but has not been explored for improving biomedical science graduate education. We assessed the TBL experience of PhD students in a graduate level immunology course. Methods: TBL sessions replaced 9 of 42 lectures in “Principles of Immunology”, a 3-credit graduate level course. Course evaluation results and student performance were compared before and after TBL implementation. Results: After TBL implementation, students gave higher ratings for the course overall, general format (teaching methods used), fairness of test grading, appropriateness of test content, and overall rating of lectures. Most students preferred TBL over other small group teaching methods, spent an hour or more preparing for class, and agreed that they were better prepared and their classmates seemed better prepared for class, and that TBL helped them prepare for exams. Most agreed that TBL resulted in more interaction and that they could learn better in TBL compared to other small group settings. Students showed modest gains in performance on exams. Conclusion: Based on student feedback, TBL appears to improve course evaluations and to promote active learning in graduate-level courses. Implementation of TBL in graduate education may improve application and problem-solving skills, generate enthusiasm in the classroom, and promote collaboration and teamwork among graduate students.
Connecting laboratories and classrooms - Easy and inexpensive educational outreach (41.4)
Authors: Lukin Kara 
Published: January 2023

Abstract
Providing high school and middle school students with first-hand scientific experiences is a powerful way in which to stimulate their interests in the biomedical sciences. Many GK-12 teachers lack the resources, personnel and/or expertise to integrate experimental procedures into their curricula. By contributing just a few hours of their time, academics at institutions of higher education can introduce simple demonstrations that will transform the manner in which students view biology and increase their academic interests and achievement. I have developed a simple, inquiry-based, lesson-plan that can be adapted readily to comply with district and/or state science standards. Investigators can adopt the exercise easily for their efforts in educational outreach. Educators seeking to incorporate novel experiences in their classrooms can accommodate the lesson to a wide range of biology courses and a diverse student population. Additionally, educators may share the lesson when soliciting scientists and professors with which to partner.
Immune modulation enhances the macrophage-mediated clearance of Pneumocystis without the severe inflammatory consequences of Pneumocystis pneumonia. (42.11)
Authors: Wang Jing , Gigliotti Frank , Bhagwat Samir , Wright Terry 
Published: January 2023

Abstract
Pneumocystis (Pc) causes high mortality Pneumocystis pneumonia (PcP) in immunocompromised patients. The Pc-driven immune response is essential for host defense against Pc. However, this response is also a key pathologic component of Immune Reconstitution Inflammatory Syndrome (IRIS), an acute form of PcP. NF-κB signaling is critical to many aspects of immune function and inflammatory responses. Its role in regulating immune-mediated inflammatory lung injury, however, is unknown. We hypothesized that specifically interrupting this pathway would diminish the Pc-driven immune response, resulting in reduced inflammatory disease at the expense of impaired immunity. As expected, when Pc-infected immunodeficient mice were immunologically reconstituted they exhibited the marked pulmonary inflammation and rapid respiratory decompensation characteristic of IRIS. In contrast, mice treated with sulfasalazine (SSZ), a potent inhibitor of IκB kinase, showed attenuated pulmonary inflammation and dramatic physiologic improvement. Unexpectedly, SSZ did not abrogate but actually enhanced the clearance of Pc from the host, while promoting an accelerated resolution of inflammatory lung disease. The enhanced Pc clearance is associated with the increased AM phagocytosis. These results suggest that a divergence exists between the mechanisms of lung injury and host defense. NF-κB and AM are potentially important therapeutic targets for the treatment of PcP.
Severe burn injury leads to spontaneous generation of Th17 CD4+ T cells in wound draining lymph nodes (42.18)
Authors: Neely Crystal , Maile Rob , Wang Ming-jin , Wolfgang Matthew , Cairns Bruce 
Published: January 2023

Abstract
Severe burn injury leads to early and prolonged immune dysfunction resulting in a reduced resistance to bacterial infection. In a model of burn injury, we have previously shown that burn mice challenged with Pseudomonas aeruginosa develop systemic infection and have high mortality rates whereas sham mice do not. Wound tissue TGF-β levels and serum IL-6 levels are elevated in the infected burn (IL-6: 32.68 +/- 9.53 pg/mL, n=4) compared to infected sham (2.87 +/- 1.43, n=3) mice. IFN-γ levels are similar between the groups. Since TGF-β and IL-6 are key for differentiation of naïve CD4+ T cells into the Th17 phenotype, we hypothesized that Th17 T cells are generated following burn injury. Female C57BL/6 mice were anesthetized and subjected to 20% full thickness contact burn or sham procedure. After 3, 7 or 14 days, CD4+ T cells selected from wound-draining lymph nodes were in vitro stimulated with mitogen. Flow cytometry was used to identify intracellular IL-17 in CD3+ CD4+ T cells. At all time points there was a statistically significant burn-dependent increase in both percentage of CD4+ T cells that were Th17 cells and absolute Th17 cell number (e.g. Day 3, 7384 +/- 1370 cells, n=3) compared to sham (1604 +/- 499, n=5). While burn injury spontaneously induces Th17 cells, known to recruit neutrophils, this does not protect against subsequent P. aeruginosa challenge. This may provide a novel mechanism for post-burn immunosuppression.
Differential response of dendritic cells to Enterococcus faecalis harboring a pathogenicity island encoded transcriptional regulator. (42.5)
Authors: Awasthi Shanjana , Baghdayan Arto , Coburn Phillip , Shankar Nathan 
Published: January 2023

Abstract
Enterococcus faecalis is responsible for the vast majority (65-80%) of nosocomial infections caused by antibiotic-resistant enterococci and treatment failure often leads to severe clinical consequences. Host immune factors can be important in preventing infection and dissemination, however, the immune mechanisms in play during E. faecalis infections are not well understood. In an earlier in vivo study, using a wild type clinical E. faecalis strain (E99) and its isogenic mutant (DBS01), deficient in a pathogenicity island encoded transcriptional regulator (PerA), we showed that the mutant strain was significantly less virulent and attenuated for survival within macrophages. In the present study we investigated how these strains interacted with dendritic cells (DCs), another key component of the innate immune system. Using flow cytometry and fluorescence microscopy we examined the phagocytic uptake of GFP-labeled E. faecalis by cultured JAWS II DCs as well as measured the expression of cell-surface DC-markers. Although, no significant differences were observed in the levels of expression of DC-markers and cytokines between the two bacterial strains, DCs phagocytosed more mutant bacteria as compared to the wild type strain. These results suggest that the virulence of strain E99 may in part be explained by its ability to circumvent the host immune system by preventing uptake and processing by DCs.