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Rancan C, Arias-Badia M, Dogra P, Chen B, Aran D, Yang H, Luong D, Ilano A, Li J, Chang H, Kwek SS, Zhang L, Lanier LL, Meng MV, Farber DL, Fong L
Nature immunology. March 18, 2023
PMID: 36928415
Columbia University
HIPC 3 (2022)
Abstract:
Gamma delta (γδ) T cells reside within human tissues including tumors, but their function in mediating antitumor responses to immune checkpoint inhibition is unknown. Here we show that kidney cancers are infiltrated by Vδ2
Wanjalla CN, Gabriel CL, Fuseini H, Bailin SS, Mashayekhi M, Simmons J, Warren CM, Glass DR, Oakes J, Gangula R, Wilfong E, Priest S, Temu T, Newell EW, Pakala S, Kalams SA, Gianella S, Smith D, Harrison DG, Mallal SA, Koethe JR
Frontiers in immunology. March 4, 2023
PMID: 36865544
cardiometabolic disease
CD4 T cells
CGC
Cytomegalovirus
HIPC 3 (2022)
HIV
Seattle Children's Research Institute
Abstract:
Persons with HIV (PWH) on long-term antiretroviral therapy (ART) have a higher incidence and prevalence of cardiometabolic diseases attributed, in part, to persistent inflammation despite viral suppression. In addition to traditional risk factors, immune responses to co-infections such as cytomegalovirus (CMV) may play an unappreciated role in cardiometabolic comorbidities and offer new potential therapeutic targets in a subgroup of individuals. We assessed the relationship of CX3CR1
Hillman H, Khan N, Singhania A, Dubelko P, Soldevila F, Tippalagama R, DeSilva AD, Gunasena B, Perera J, Scriba TJ, Ontong C, Fisher M, Luabeya A, Taplitz R, Seumois G, Vijayanand P, Hedrick CC, Peters B, Burel JG
Frontiers in immunology. Jan. 31, 2023
PMID: 36713384
Flow Cytometry
HIPC 3 (2022)
immune signatures
La Jolla Institute for Immunology
Monocytes
transcriptomics (RNA-Seq)
Tuberculosis
Abstract:
Previous studies suggest that monocytes are an important contributor to tuberculosis (TB)-specific immune signatures in blood.
Here, we carried out comprehensive single-cell profiling of monocytes in paired blood samples of active TB (ATB) patients at diagnosis and mid-treatment, and healthy controls.
At diagnosis, ATB patients displayed increased monocyte-to-lymphocyte ratio, increased frequency of CD14+CD16- and intermediate CD14+CD16+ monocytes, and upregulation of interferon signaling genes that significantly overlapped with previously reported blood TB signatures in both CD14+ subsets. In this cohort, we identified additional transcriptomic and functional changes in intermediate CD14+CD16+ monocytes, such as the upregulation of inflammatory and MHC-II genes, and increased capacity to activate T cells, reflecting overall increased activation in this population. Single-cell transcriptomics revealed that distinct subsets of intermediate CD14+CD16+ monocytes were responsible for each gene signature, indicating significant functional heterogeneity within this population. Finally, we observed that changes in CD14+ monocytes were transient, as they were no longer observed in the same ATB patients mid-treatment, suggesting they are associated with disease resolution.
Together, our study demonstrates for the first time that both intermediate and classical monocytes individually contribute to blood immune signatures of ATB and identifies novel subsets and associated gene signatures that may hold disease relevance.
Poon MML, Caron DP, Wang Z, Wells SB, Chen D, Meng W, Szabo PA, Lam N, Kubota M, Matsumoto R, Rahman A, Luning Prak ET, Shen Y, Sims PA, Farber DL
Nature immunology. Jan. 20, 2023
PMID: 36658238
Columbia University
HIPC 3 (2022)
Abstract:
T lymphocytes migrate to barrier sites after exposure to pathogens, providing localized immunity and long-term protection. Here, we obtained blood and tissues from human organ donors to examine T cells across major barrier sites (skin, lung, jejunum), associated lymph nodes, lymphoid organs (spleen, bone marrow), and in circulation. By integrating single-cell protein and transcriptome profiling, we demonstrate that human barrier sites contain tissue-resident memory T (T
Konstorum A, Mohanty S, Zhao Y, Melillo A, Vander Wyk B, Nelson A, Tsang S, Blevins TP, Belshe RB, Chawla DG, Rondina MT, Gill TM, Montgomery RR, Allore HG, Kleinstein SH, Shaw AC
Aging cell. Jan. 20, 2023
PMID: 36656789
age-specific immunity
Blood Platelets
Flow Cytometry
Frailty
HIPC 3 (2022)
Immunosenescence
RNAseq
tensor decomposition
Vaccination
Yale University
Abstract:
Platelets are uniquely positioned as mediators of not only hemostasis but also innate immunity. However, how age and geriatric conditions such as frailty influence platelet function during an immune response remains unclear. We assessed the platelet transcriptome at baseline and following influenza vaccination in Younger (age 21-35) and Older (age ≥65) adults (including community-dwelling individuals who were largely non-frail and skilled nursing facility (SNF)-resident adults who nearly all met criteria for frailty). Prior to vaccination, we observed an age-associated increase in the expression of platelet activation and mitochondrial RNAs and decrease in RNAs encoding proteins mediating translation. Age-associated differences were also identified in post-vaccination response trajectories over 28 days. Using tensor decomposition analysis, we found increasing RNA expression of genes in platelet activation pathways in young participants, but decreasing levels in (SNF)-resident adults. Translation RNA trajectories were inversely correlated with these activation pathways. Enhanced platelet activation was found in community-dwelling older adults at the protein level, compared to young individuals both prior to and post-vaccination; whereas SNF residents showed decreased platelet activation compared to community-dwelling older adults that could reflect the influence of decreased translation RNA expression. Our results reveal alterations in the platelet transcriptome and activation responses that may contribute to age-associated chronic inflammation and the increased incidence of thrombotic and pro-inflammatory diseases in older adults.
Shook LL, Edlow AG
Obstetrics and gynecology. Jan. 18, 2023
PMID: 36649326
HIPC 3 (2022)
Massachusetts Institute of technology
Abstract:
In this review, we summarize the data on the safety and side-effect profile of coronavirus disease 2019 (COVID-19) vaccines during lactation to date, review what is known about mRNA vaccine components in breast milk, and discuss the efficacy of COVID-19 vaccines in providing immune protection for the breastfeeding infant. The Centers for Disease Control and Prevention and the American College of Obstetricians and Gynecologists recommend that lactating individuals receive COVID-19 mRNA vaccines and stay up to date on booster doses, including the bivalent COVID-19 booster. The lack of serious side effects in mothers or infants across numerous large studies and registries of COVID-19 vaccination in pregnancy and lactation is reassuring. Although small quantities of mRNA may be transiently detectable in breast milk after maternal vaccination, there are no data demonstrating that vaccine mRNA can survive the infant gastrointestinal tract and no evidence that breast milk from lactating individuals who have received a COVID-19 mRNA vaccine can cause harm to breastfeeding infants. In contrast, numerous studies demonstrate that the breast milk of vaccinated individuals contains severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific functional antibodies and T cells, which benefit the breastfeeding infant's developing immune system. Transfer of SARS-CoV-2-specific antibodies from mother to infant is highest when vaccination occurs during pregnancy compared with lactation, because the breastfeeding infant receives both long-lasting antibodies through the placenta and breast-milk antibodies through breast milk. With clear data demonstrating efficacy and safety and no data demonstrating harm to mother or infant after COVID-19 vaccine administration during lactation, any recommendations to avoid vaccination while breastfeeding or to withhold breast milk from the infant for any period of time after vaccination are not supported by available evidence.
Shinoda K, Li R, Rezk A, Mexhitaj I, Patterson KR, Kakara M, Zuroff L, Bennett JL, von Büdingen HC, Carruthers R, Edwards KR, Fallis R, Giacomini PS, Greenberg BM, Hafler DA, Ionete C, Kaunzner UW, Lock CB, Longbrake EE, Pardo G, Piehl F, Weber MS, Ziemssen T, Jacobs D, Gelfand JM, ...
Proceedings of the National Academy of Sciences of the United States of America. Jan. 13, 2023
PMID: 36634138
anti-CD20 therapy
CD20-expressing T cells
CD20dim T cells
CD20dimCD8+ T cells
HIPC 3 (2022)
ocrelizumab
Yale University
Abstract:
A small proportion of multiple sclerosis (MS) patients develop new disease activity soon after starting anti-CD20 therapy. This activity does not recur with further dosing, possibly reflecting deeper depletion of CD20-expressing cells with repeat infusions. We assessed cellular immune profiles and their association with transient disease activity following anti-CD20 initiation as a window into relapsing disease biology. Peripheral blood mononuclear cells from independent discovery and validation cohorts of MS patients initiating ocrelizumab were assessed for phenotypic and functional profiles using multiparametric flow cytometry. Pretreatment CD20-expressing T cells, especially CD20
Asashima H, Mohanty S, Comi M, Ruff WE, Hoehn KB, Wong P, Klein J, Lucas C, Cohen I, Coffey S, Lele N, Greta L, Raddassi K, Chaudhary O, Unterman A, Emu B, Kleinstein SH, Montgomery RR, Iwasaki A, Dela Cruz CS, Kaminski N, Shaw AC, Hafler DA, Sumida TS
Cell reports. Jan. 4, 2023
PMID: 36596303
CP: Immunology
CXCR3(+) plasmablasts
HIPC 3 (2022)
IFNγ
PD-1(high)CXCR5(–)CD4(+) peripheral helper T cells
T cell-B cell interactions
Tph cells
Yale University
Abstract:
T cell-B cell interaction is the key immune response to protect the host from severe viral infection. However, how T cells support B cells to exert protective humoral immunity in humans is not well understood. Here, we use COVID-19 as a model of acute viral infections and analyze CD4
Duffy FJ, Hertoghs N, Du Y, Neal ML, Oyong D, McDermott S, Minkah N, Carnes J, Schwedhelm KV, McElrath MJ, De Rosa SC, Newell E, Aitchison JD, Stuart K
Frontiers in immunology. Jan. 3, 2023
PMID: 36591224
high parameter flow cytometry
HIPC 3 (2022)
Immunophenotyping
Malaria
radiation-attenuated sporozoites
Seattle Children's Research Institute
serum antibody profiling
systems immunology
Vaccines
whole blood transcriptional profiling
Abstract:
Identifying immune processes required for liver-stage sterilizing immunity to malaria remains an open problem. The IMRAS trial comprised 5x immunizations with radiation-attenuated sporozoites resulting in 55% protection from subsequent challenge.
To identify correlates of vaccination and protection, we performed detailed systems immunology longitudinal profiling of the entire trial time course including whole blood transcriptomics, detailed PBMC cell phenotyping and serum antigen array profiling of 11 IMRAS radiation-attenuated sporozoite (RAS) vaccinees at up to 21 timepoints each.
RAS vaccination induced serum antibody responses to CSP, TRAP, and AMA1 in all vaccinees. We observed large numbers of differentially expressed genes associated with vaccination response and protection, with distinctly differing transcriptome responses elicited after each immunization. These included inflammatory and proliferative responses, as well as increased abundance of monocyte and DC subsets after each immunization. Increases in Vδ2 γδ; T cells and MAIT cells were observed in response to immunization over the course of study, and CD1c+ CD40+ DC abundance was significantly associated with protection. Interferon responses strongly differed between protected and non-protected individuals with high interferon responses after the 1
This study has revealed multiple coordinated immunological processes induced by vaccination and associated with protection. Our work represents the most detailed immunological profiling of a RAS vaccine trial performed to date and will guide the design and interpretation of future malaria vaccine trials.
Boada P, Fatou B, Belperron AA, Sigdel TK, Smolen KK, Wurie Z, Levy O, Ronca SE, Murray KO, Liberto JM, Rashmi P, Kerwin M, Montgomery RR, Bockenstedt LK, Steen H, Sarwal MM
Frontiers in immunology. Dec. 27, 2022
PMID: 36569838
Acute-Phase Reaction
Asymptomatic Infections
HIPC 3 (2022)
Immune System
localized and disseminated stage
longitudinal analysis
Lyme Disease
serum proteomics
West Nile virus
Yale University
Abstract:
Advancement in proteomics methods for interrogating biological samples has helped identify disease biomarkers for early diagnostics and unravel underlying molecular mechanisms of disease. Herein, we examined the serum proteomes of 23 study participants presenting with one of two common arthropod-borne infections: Lyme disease (LD), an extracellular bacterial infection or West Nile virus infection (WNV), an intracellular viral infection. The LC/MS based serum proteomes of samples collected at the time of diagnosis and during convalescence were assessed using a depletion-based high-throughput shotgun proteomics (dHSP) pipeline as well as a non-depleting blotting-based low-throughput platform (MStern). The LC/MS integrated analyses identified host proteome responses in the acute and recovery phases shared by LD and WNV infections, as well as differentially abundant proteins that were unique to each infection. Notably, we also detected proteins that distinguished localized from disseminated LD and asymptomatic from symptomatic WNV infection. The proteins detected in both diseases with the dHSP pipeline identified unique and overlapping proteins detected with the non-depleting MStern platform, supporting the utility of both detection methods. Machine learning confirmed the use of the serum proteome to distinguish the infection from healthy control sera but could not develop discriminatory models between LD and WNV at current sample numbers. Our study is the first to compare the serum proteomes in two arthropod-borne infections and highlights the similarities in host responses even though the pathogens and the vectors themselves are different.
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Last updated: 2023-03-22 18:30