About

Nicole Baumgarth, DVM, PhD, is an Immunologist and the Bloomberg Distinguished Professor at Johns Hopkins Bloomberg School of Public Health. She leads efforts to eliminate threats from tickborne diseases, such as Lyme disease, and studies why some immune responses to infections are successful while others are not. Her research focuses on immunity to infections with Borrelia burgdorferi, the causative agent of Lyme disease, and influenza virus. She is the inaugural director of the Lyme and Tickborne Diseases Research and Education Institute. Dr. Baumgarth has a background in veterinary medicine and immunology, with education from the School of Veterinary Medicine in Hannover. Her research interests include antibodies, B cell subsets, host-pathogen interactions, humoral immunity, and host response mechanisms. She has received numerous honors and awards, including the Neil L. Spector Memorial Award, election as a Fellow of the AAAS, and the Zoetis Excellence in Research Award. Her work has contributed significantly to understanding B cell responses and immune regulation in infectious diseases, with a focus on Lyme disease and influenza.

Research topics

• Immunology
• Intensive care medicine
• Medicine
• Pathology

Selected publications

• Age-driven shifts in T and NK cell responses amplify inflammation and coagulopathy during viral infection in mice and humans

  Frontiers in Immunology · 2026-02-09 · 1 citations

  articleOpen access

  Introduction: Advanced age is associated with increased morbidity and mortality following acute viral infections, including SARS-CoV-2. Despite this, most preclinical models rely on young animals and fail to account for age-related immune remodeling. How advanced aging alters antiviral immune responses and contributes to immune-mediated pathology remains incompletely understood. Methods: Young (2-6 months), aged (15-18 months), and advanced aged (20-29 months) mice were infected with murine cytomegalovirus (MCMV) or influenza virus. Survival, viral burden, cytokine production, immune cell phenotypes, and tissue pathology were assessed using flow cytometry, histology, serum cytokine analysis, and RNA sequencing. Mouse findings were compared with publicly available transcriptomic datasets from SARS-CoV-2-infected human cohorts across age groups. Results: Advanced aged mice exhibited markedly increased mortality and organ pathology following viral infection despite maintaining viral loads comparable to younger mice. These outcomes were associated with heightened systemic and tissue inflammatory cytokine production, reduced antigen-specific T cell responses, and increased frequencies of NK cells and non-antigen-specific bystander T cell activation. Coagulopathy with thrombolytic clot formation was observed exclusively in advanced aged mice. Transcriptomic analysis revealed enrichment of inflammatory and coagulation pathways in influenza-infected advanced aged mice, paralleling findings in elderly humans with SARS-CoV-2 infection, who also displayed reduced expression of T cell-associated genes. Discussion: These findings demonstrate that advanced age profoundly alters antiviral immune responses, shifting immunity away from effective antigen-specific T cell responses toward inflammatory and innate pathways that contribute to immune-mediated pathology. The results highlight the importance of modeling advanced aging in preclinical studies and suggest that age-dependent immune imbalance may underlie increased inflammation, coagulopathy, and mortality during viral infection in both mice and humans.

  PublisherDOI

• The Presence of CD11c+ B Cells with Potent Effector Memory Phenotype in Lung Adenocarcinoma Correlates with Overall Patient Survival

  Cancer Immunology Research · 2026-02-13

  articleOpen accessSenior author

  Tumor-infiltrating B lymphocytes (TIL-B) are increasingly recognized as favorable prognostic markers in multiple cancer types, and the mechanisms underlying this are being actively investigated. In this study of TIL-Bs, we identified CD79A as a reliable quantifier of B lymphocytes and evaluated transcriptomic data for 15 distinct tumors using 8,720 samples of treatment naïve patients from The Cancer Genome Atlas and normal tissues from Gene Tissue Expression. B-lymphocyte infiltration correlated with survival for some but not all tumors. In lung adenocarcinoma (LUAD), CD79A levels were strongly predictive of overall survival, whereas CD8A transcripts were not, indicating that leukocytic infiltration per se does not explain the B cell's impact. Single-cell RNA sequencing and flow cytometry identified increased relative numbers of CD11c+ B cells in patients with treatment-naïve LUAD compared with normal tissue and blood. In LUAD, CD11c+ TIL-Bs were localized near CD4+ T cells, and in vitro stimulation with anti-IgG with/without CD40 agonist resulted in expansion and rapid differentiation. Stimulation also induced IL12, IL21, and TNFα secretion, which are cytokines known to enhance antitumor immunity. Overall, the data indicate that CD11c+ TIL-Bs are a potential target for anticancer therapeutic approaches and/or a potential prognostic biomarker for cancer prognosis.

  PublisherOA PDFDOI

• Extrafollicular B Cell Responses—Is One Tent Big Enough?

  Immunological Reviews · 2025-11-01 · 3 citations

  reviewOpen access1st authorCorresponding

  Initial description of extrafollicular B cell responses (EF) identified them as short-lived clusters of rapidly proliferating B cells and plasmablasts in splenic bridging channels and red pulp as well as lymph node medullary cord areas. Their physical location guided the nomenclature: outside, or at the edges of B cell follicles and near T cell zones of secondary lymphoid organs, thus distinct from the follicular situated germinal centers (GCs). Because EFs are often induced transiently and to both T-dependent and T-independent antigens, and because they generate IgM and class-switched antibodies often with no or little signs of somatic hypermutations, they were thought to be less impactful than GC-derived antibodies. However, highly protective antibodies are generated by these EFs rapidly after acute infections and their induction often correlates with pathogen clearance, while in autoimmunity EF-derived antibodies have been implicated as pathogenic drivers of disease. Moreover, subsets of memory B cells, including some CD11c+ "atypical" B cells/ABCs are generated independently of GC. Their diverse appearance and impact have initiated an ongoing debate about whether all "non-GC responses" are necessarily EF responses. The current debate is reflected also in the articles compiled for this issue of Immunological Reviews considering EF responses. Here, I briefly summarize the steps leading to B cell activation and EF and GC formation, providing context for the contributed reviews that span a breadth of topics from descriptions of non-GC responses in jawed non-mammalian vertebrates as possible orthologues of mammalian EF to the molecular and metabolic requirements and CD4 T cell helper quality of EF, tissue-specific B cell responses, and discussions on the origins and classifications of "atypical" memory B cells in mice and man.

  PublisherOA PDFDOI

• B cell intrinsic TLR3 and TLR7 signaling synergistically enhance B cell differentiation during influenza infection-induced extrafollicular responses 3781

  The Journal of Immunology · 2025-11-01

  articleOpen accessSenior author

  Abstract Description The extrafollicular (EF) B cell response induces virus-neutralizing, class switched antibodies rapid enough to impact influenza virus clearance after acute infection. Previously we showed that MyD88 and TRIF are both required for robust EF responses, acting in a B cell intrinsic manner. While MyD88 was shown previously to affect B cell activation, how TRIF and its upstream receptor(s) support EF responses is unknown. To address this, MyD88-/- TLR3-/- double-deficient total and B cell-specific KO mice were infected with influenza A/PR/8 (IAV) alongside controls. Both, global and B cell-intrinsic MyD88-/-TLR3-/- double-deficient mice had significantly reduced EF-derived B cells, plasma cells (PCs), and hemagglutinin (HA)+ EF-derived PCs and reduced IAV-specific serum IgG post-infection days 7 and 9, respectively, indicating a critical role for TLR3 in early B cell stimulation. Consistent with these findings, stimulation of negatively enriched naïve splenic B cells with TLR3 ligand POLY(I:C) induced surface expression of CD25, CD69, and CD86 by 24 hours of culture but not proliferation, while the combined stimulation with POLY(I:C) and TLR7 agonist (CL097), significantly and synergistically increased proliferation and BLIMP+ CD138+ PC differentiation by 96 hours. Together this data shows a novel role for B cell intrinsic TRIF/TLR3, in B cell differentiation when combined with a second, MyD88-dependent agonist. Funding Sources This work was supported by NIH R01 AI117890, AI184867 (to NB) and NIH T32 HL007013-40 (to EJK and JHL). Topic Categories Immune Response Regulation: Cellular Mechanisms (IRC)

  PublisherOA PDFDOI

• Extravasation of <i>Borrelia burgdorferi</i> Across the Blood–Brain Barrier is an Extremely Rare Event

  Advanced Science · 2025-03-12 · 3 citations

  articleOpen access

  Lyme disease, the most widespread tick-borne disease in North America, is caused by the bacterium Borrelia burgdorferi (Bb). Approximately 10-15% of infections result in neuroborreliosis, common symptoms of which include headaches, facial palsy, and long-term cognitive impairment. Previous studies of Bb dissemination focus on assessing Bb transmigration at static time points rather than analyzing the complex dynamic process of extravasation. Furthermore, current in vitro models lack crucial physiological factors such as flow, demonstrating a need for more robust models for studying Bb dissemination to understand its dynamics and mechanisms. Here, a 3D tissue-engineered microvessel model is used and fluorescently-labeled Bb is perfused to model vascular dissemination in non-tissue-specific (iEC) and brain-specific (iBMEC) microvessels while acquiring time-lapse images in real time. In iECs, extravasation involves two steps: adhesion to the endothelium and transmigration into the extracellular matrix, which can be modulated through glycocalyx degradation or inflammation. In contrast, Bb extravasation in iBMECs is an extremely rare event regardless of glycocalyx degradation or inflammation. In addition, circulating Bb do not induce endothelial activation in iECs or iBMECs, but induces barrier dysfunction in iECs. These findings provide a further understanding of Bb vascular dissemination.

  PublisherOA PDFDOI

• A roadmap for defining “extrafollicular” B cell responses

  Immunity · 2025-09-23 · 18 citations

  reviewSenior author
  PublisherDOI

• B cells modulate lung antiviral inflammatory responses via the neurotransmitter acetylcholine

  Nature Immunology · 2025-04-22 · 18 citations

  articleOpen accessSenior author

  The rapid onset of innate immune defenses is critical for early control of viral replication in an infected host and yet it can also lead to irreversible tissue damage, especially in the respiratory tract. Sensitive regulators must exist that modulate inflammation, while controlling the infection. In the present study, we identified acetylcholine (ACh)-producing B cells as such early regulators. B cells are the most prevalent ACh-producing leukocyte population in the respiratory tract demonstrated with choline acetyltransferase (ChAT)-green fluorescent protein (GFP) reporter mice, both before and after infection with influenza A virus. Mice lacking ChAT in B cells, disabling their ability to generate ACh (ChatBKO), but not those lacking ChAT in T cells, significantly, selectively and directly suppressed α7-nicotinic-ACh receptor-expressing interstitial, but not alveolar, macrophage activation and their ability to secrete tumor necrosis factor (TNF), while better controlling virus replication at 1 d postinfection. Conversely, TNF blockade via monoclonal antibody treatment increased viral loads at that time. By day 10 of infection, ChatBKO mice showed increased local and systemic inflammation and reduced signs of lung epithelial repair despite similar viral loads and viral clearance. Thus, B cells are key participants of an immediate early regulatory cascade that controls lung tissue damage after viral infection, shifting the balance toward reduced inflammation at the cost of enhanced early viral replication.

  PublisherOA PDFDOI

• Deciphering TLR3 and TLR7-mediated control of extrafollicular B cell proliferation and plasma cell differentiation 4202

  The Journal of Immunology · 2025-11-01

  articleOpen accessSenior author

  Abstract Description Extrafollicular (EF) B cell responses are essential for protective immunity, but the signals that direct naïve B cells toward an EF fate remain unclear. Our previous work showed that deleting both adaptor proteins, MyD88 and TRIF, reduced EF cell numbers post-influenza infection. In separate studies, we show that TLR3 activation appears to be upstream of TRIF and TLR7 activation upstream of MyD88 signaling, but what role each of these adaptor proteins play in EF formation remains undefined. To address this, we performed flow cytometric analysis of CTV-labeled naïve B cells stimulated with TLR3, TLR7, or combined TLR3 + 7 agonists over a 96-hour period. Stimulation through TLR7 (CL097) promoted robust proliferation without plasma-cell differentiation, while TLR3 stimulation (POLY(I:C)) induced activation, as measured by increased cell surface expression of co-stimulatory receptors. Notably, TLR3 + 7 co-stimulation synergistically enhanced both proliferation and plasma-cell differentiation. qPCR analysis of key plasma-cell differentiation factors, including Pax5, Bach2, BLIMP1 and IRF4, all of which were strongly upregulated by combined TLR3 + 7 stimulation. To further dissect the transcriptional targets downstream of each TLR signal alone or in combination, we are using bulk RNA-Seq analysis with the goal to delineate the signaling pathways that explain the synergistic effects of these two distinct TLR stimuli on the kinetics of plasma cell differentiation in vitro. Funding Sources Funding sources: R01AI148652 and R01AI184867 Topic Categories Immune Response Regulation: Molecular Mechanisms (IRM)

  PublisherOA PDFDOI

• B cells modulate lung antiviral inflammatory responses via the neurotransmitter acetylcholine

  Research Square · 2024-06-25

  preprintOpen access1st authorCorresponding

  The rapid onset of innate immune defenses is critical for early control of viral replication in an infected host, yet it can also lead to irreversible tissue damage, especially in the respiratory tract. Intricate regulatory mechanisms must exist that modulate inflammation, while controlling the infection. Here, B cells expressing choline acetyl transferase (ChAT), an enzyme required for production of the metabolite and neurotransmitter acetylcholine (ACh) are identified as such regulators of the immediate early response to influenza A virus. Lung tissue ChAT + B cells are shown to interact with a7 nicotinic Ach receptor-expressing lung interstitial macrophages in mice within 24h of infection to control their production of TNFa, shifting the balance towards reduced inflammation at the cost of enhanced viral replication. Thus, innate-stimulated B cells are key participants of an immediate-early regulatory cascade that controls lung tissue damage after viral infection.

  PublisherOA PDFDOI

• Boosting immunity to protect from tickborne Lyme disease

  The Lancet Infectious Diseases · 2024-07-16 · 1 citations

  articleOpen access1st authorCorresponding
  PublisherOA PDFDOI

Recent grants

• Comparative Medical Science Training Program

  NIH · $5.5M · 1988–2027

• NIH Grant R01AI055881

  NIH · $1.5M · 2008

• NIH Grant P01DE016839

  NIH · $4.4M · 2009

• Regulation of anti-viral CD8+ responses via adhesion molecules

  NIH · $24.1M · 2020

• NIH Grant R01AI073911

  NIH · $1.9M · 2014

Frequent coauthors

• Jonathan Lam

  Massachusetts Institute of Technology

  18 shared

• Leonore A. Herzenberg

  14 shared

• Zheng Luo

  Ministry of Agriculture and Rural Affairs

  13 shared

• Kimberly J. Olsen

  University of California, Davis

  12 shared

• Richard Szubin

  La Jolla Bioengineering Institute

  12 shared

• Ometa C. Herman

  11 shared

• Hannah P. Savage

  University of California, Davis

  10 shared

• Rosemarie H. DeKruyff

  Stanford University

  10 shared

Education

• post-doctoral fellow

  Queeensland Institute of Medical Research

  1996

• post-doctoral fellow

  Walter and Eliza Hall Institute of Medical Research

  1992

• PhD, Dept of Microbiology

  School of Veterinary Medicine Hannover

  1989

• DVM

  School of Veterinary Medicine Hannover

  1986

Awards & honors

• Neil L. Spector Memorial Award (2021)
• Lauren Brooks Hope Award (2019)
• Zoetis Excellence in Research Award (2018)
• UC Davis Chancellor’s Fellow (2008 - 2012)
• Carl Norden Prize for most outstanding research during postg…