Norwegian Society for Immunology (NSI)

In our next NSI Rising Star Seminar, we will be hosting Clarissa Campbell (CeMM, Austrian Academy of Sciences) with a talk on “T cell regulation by bacterial metabolites”. Look forward to seeing you there!

Meeting details:
Monday 7th October at 13:00
https://uio.zoom.us/j/62979749183?pwd=l2eOW7eqdaGiBElGJaWYy2VskyWe76.1
Meeting ID: 629 7974 9183
Passcode: 237779

Title of talk: T cell regulation by bacterial metabolites

Abstract:
Intestinal microbial communities expand the functional capabilities of the host via their metabolic attributes. From energy harvest to the production of vitamins, the gut microbiota shapes mammalian physiology and is often considered a postnatally developed “organ”. Yet, the microbiome poses a formidable challenge to the immune system: How can we host trillions of bacteria without mounting an inflammatory response? Gut immune homeostasis relies on the balanced action of suppressive and inflammatory T cell subsets. Using transgenic mouse models, engineered bacteria and gnotobiotic experiments, we discovered that common products of bacterial metabolism including short-chain fatty acids and microbe-derived bile acids affect the differentiation of Foxp3+ immunosuppressive regulatory T (Treg) cells at the steady state. Further, we found that Treg cells induced in response to bacterial cues support the establishment and maintenance of intestinal microbial communities. More recently, we discovered that intestinal inflammation leads to the loss of microbe-derived bile acids, thus contributing to fuel T cell-driven pathologies. Altogether, our work uncovered a prominent role for microbial metabolites in shaping host immunity by modulating T cell responses both at the steady state and during inflammatory settings.

Bio:
Clarissa Campbell studied biology with a minor in genetics at the Federal University of Rio de Janeiro (UFRJ) and subsequently earned a master’s degree from the Oswaldo Cruz Foundation (FIOCRUZ), investigating how bacterial molecules exert immunomodulatory effects on mammalian cells via nuclear receptors, a topic she would continue to explore throughout her career. She joined the Tri-Institutional Immunology and Microbial Pathogenesis Program at Weill Cornell Medical College in New York as a graduate student where she specialized in mucosal immunology and regulatory T (Treg) cell biology. After obtaining her PhD, Clarissa Campbell remained under the mentorship of Dr. Alexander Rudensky at Memorial Sloan Kettering Cancer Center to continue her work on host-commensal interactions and pursue broader scientific questions bridging the fields of immunology and metabolism. Her research has characterized a circuit whereby microbial metabolites including short-chain fatty acids and secondary bile acids facilitate the differentiation of peripherally induced Treg cells, which in turn suppress immune responses to colonization and preserve a niche for a group of intestinal bacteria. More recently, she found that a bile acidsensing nuclear receptor contributes to the cell-intrinsic responsiveness of effector T cells to fasting. Clarissa Campbell joined CeMM as a principal investigator in July 2021. Her lab is interested in investigating how changes in microbial and organismal metabolism contribute to regulating immune-cell function.

Key publications:

1. Nuclear receptor LXRβ controls fitness and functionality of activated T cells. J Exp Med. 2021
2. FXR mediates T cell-intrinsic responses to reduced feeding during infection. Proc Natl Acad Sci USA. 2020
3. Bacterial metabolism of bile acids promotes generation of peripheral regulatory T cells. Nature. 2020

In our next seminar from the NSI Rising Star Seminar series, we will be hosting Abigail Vanderheiden (Washington University in St. Louis, Missouri, USA) with a talk on “ Investigating the contribution of the immune response to memory deficits after COVID-19 in mice”.
Look forward to seeing you there!

Meeting details:
Thursday, 5. September, 15.00
https://uio.zoom.us/j/65066940943?pwd=CX8za4Wa20jZLAib9fHOXQzQzzanRn.1

Abstract: 
Millions of patients with post-acute symptoms of COVID-19 or ‘long-COVID’ are accumulating worldwide, however, the underlying mechanisms driving neurological dysfunction and how vaccination impacts risk are unknown. Current evidence suggests that SARS-CoV-2 does not cause widespread infection of the central nervous system (CNS). Despite this, post-mortem analyses of the hippocampi of COVID-19 patients have identified microglial activation, decreased neurogenesis, blood-brain barrier disruption, and pro-inflammatory cytokine production, including Interleukin-1b (IL-1b) a key component of the innate immune defense against viral infection. Here, we utilize a novel mouse model of the neurological effects of COVID-19 to investigate how innate immunity impacts memory deficits after SARS-CoV-2. We find that intranasal infection of C57BL/6J mice with the beta variant of SARS-CoV-2 (B.1.351) causes post-acute memory deficits as measured via the Novel Object recognition test that correlate with decreases in hippocampal neurogenesis and trisynaptic circuit synapse number. We find that SARS-CoV-2 infection prompts peripheral immune cell infiltration, persistent microglial activation, and elevated levels of IL-1b in the hippocampus. Mechanistically, we demonstrate that IL-1R1 signaling on neural stem cells promotes loss of hippocampal neurogenesis and subsequent memory deficits after SARS-CoV-2. Vaccination with a low dose of adenoviral vectored Spike protein prevents production of IL-1b in the hippocampus and subsequently protects against loss of neurogenesis and memory deficits after breakthrough SARS-CoV-2 infection. Combined, these data identify microglial production of IL-1b as one pathway driving memory deficits after COVID-19 that can be prevented by prior vaccination.

Bio: 
Dr. Vanderheiden is a post-doctoral research scholar in the laboratory of Dr. Michael Diamond at Washington University in St. Louis, Missouri, USA. Dr. Vanderheiden performed her Ph.D. work in Immunology under the mentorship of Dr. Mehul Suthar at Emory University (Atlanta, GA, USA) where she investigated innate immune signaling in response to West Nile virus and SARS-CoV-2 and helped develop a novel mouse model of SARS-CoV-2 infection. She began her post-doctoral training under Dr. Robyn Klein at Washington University in St. Louis, where she used this mouse model to investigate how IL-1 signaling promotes memory deficits after COVID-19. In 2023, Dr. Klein left Washington University and Dr. Vanderheiden moved to the lab of Dr. Michael S. Diamond do continue her post-doctoral studies on how the immune response to SARS-CoV-2 infection impacts post-acute neurological dysfunction after COVID-19.

Key publications:
1. “Vaccination reduces central nervous system IL-1β and memory deficits after COVID-19 in mice.” Nature Immunology (2024): 1-14.
2. “COVID-19 induces CNS cytokine expression and loss of hippocampal neurogenesis.” Brain 145.12 (2022): 4193-4201.
3. “Type I and type III interferons restrict SARS-CoV-2 infection of human airway epithelial cultures.” Journal of virology 94.19 (2020): 10-1128.

In our next seminar from the NSI Rising Star Seminar series, we will be hosting Camilla Engblom (Karolinska Institutet, Stockholm, Sweden) with a talk on “Mapping B and T cell receptors in tissues using spatial transcriptomics”.
Look forward to seeing you there!

Meeting details:
Thursday, 15. august, 13.00
https://uib.zoom.us/j/64667274238?pwd=aNkElnisAOMYP9WaMaVbaGb5lXtG0L.1
Meeting ID: 646 6727 4238
Password: guf3QPtA

Abstract: 
B and T cells perform functions critical to human health and they develop, differentiate, and expand in spatially distinct sites across the body. Both B and T cells express clonal heritable antigen receptors that confer exquisite molecular (i.e., antigen) specificity. Antigen receptors can be defined by sequencing, but these methods require tissue dissociation, which loses the anatomical location, and the surrounding functionally relevant environmental cues. Linking specific clonal sequences to their molecular and cellular surroundings, i.e., ‘clonal niche’, could help us understand and harness B and T cell activity. A technological bottleneck has been to capture the location of antigen receptor sequences, and by extension B and T cell clonal responses, directly within tissues. To address this, we recently developed a spatial transcriptomics-based approach (Spatial VDJ) and associated computational pipelines to reconstruct B and T cell clonality in human tissues. Using this technology, we spatially resolve B and T cell receptors within immune and tumor tissues, as well as B cell clonal evolution within germinal centers. Combined, Spatial VDJ links B and T cell clonal responses to their microenvironment with applications to various immune-related pathologies, including infections, cancer and autoimmune diseases. 

Bio: 
Dr. Camilla Engblom is a SciLifeLab Fellow and a recently appointed Assistant Professor in the Division of Immunology and Allergy and the Department of Medicine, Solna at the Karolinska Institutet (KI). She received her PhD in Immunology from Harvard University in 2017 focusing on long-range cancer-host interactions involving myeloid cells (Mikael Pittet’s lab at Massachusetts General Hospital/Harvard Medical School). As a MSCA postdoctoral fellow in Jonas Frisén’s lab (KI) in a collaboration with Joakim Lundeberg’s lab, Dr. Engblom developed a spatial transcriptomics-based tool (Spatial VDJ) to map B cell and T cell receptors within human tissues. Located at SciLifeLab and the Center for Molecular Medicine (KI), the Engblom lab’s main research focus is to spatially and functionally resolve B cell clonal dynamics during cancer.

Key publications:

1. C. Engblom*/K. Thrane*/Q. Lin*, et al. Science. (2023).
2. Zilionis R*, Engblom C*, Pfirschke C*, Savova V*, et al. Immunity. 2019. May 21;50(5):1317-1334.
3. Engblom C*, Pfirschke C, et al. Science. 2017 Dec 1;358(6367).
4. Pfirschke C*, Engblom C*, et al. Immunity. 2016 Feb 16;44(2):343-54.