Article
Biology
Thomas P. Burke, Patrik Engstrom, Cuong J. Tran, Ingeborg M. Langohr, Dustin R. Glasner, Diego A. Espinosa, Eva Harris, Matthew D. Welch
Summary: Mice lacking both interferon receptors provide a tractable model for investigating rickettsiosis, virulence factors, and immunity. The study shows that the actin-based motility factor Sca2 is required for dissemination from the skin to internal organs, and the outer membrane protein OmpB contributes to eschar formation, revealing potential live-attenuated vaccine candidates. Differences in interferon signaling may underlie the discrepancies in susceptibility to rickettsial pathogens between mice and humans.
Article
Nutrition & Dietetics
Fei Wang, Chih-Wei Ko, Jie Qu, Dong Wu, Qi Zhu, Min Liu, Patrick Tso
Summary: Apolipoprotein A-IV (apoA-IV) plays an important role in regulating lipid absorption and metabolism, food intake, and glucose metabolism. This study found that apoA-IV knockout mice on the 129/SvJ background became significantly more obese and insulin-resistant than wild-type mice when fed a high-fat diet. These results underscore the impact of genetic background on the metabolic effects of apoA-IV.
Article
Immunology
Marcelo Pires Amaral, Felipe Daniel Cardoso, Ingrid Sancho de Farias, Rafael Queiroz de Souza, Kely Catarine Matteucci, Ana Claudia Torrecilhas, Karina Ramalho Bortoluci
Summary: This study investigated the activation of the NAIP/NLRC4 inflammasome in response to Trypanosoma cruzi infection. The results showed that NAIP and NLRC4 proteins are required for IL-1 beta and NO release in response to T. cruzi infection, and their absence allows for parasite replication in macrophages. Furthermore, Nlrc4 (-/-) and Nlrp3(-/-) macrophages exhibited similar impaired responses to T. cruzi infection, highlighting the non-redundant roles played by these inflammasomes in the context of infection.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Anna M. Gram, John A. Wright, Robert J. Pickering, Nathaniel L. Lam, Lee M. Booty, Steve J. Webster, Clare E. Bryant
Summary: The study demonstrates that flagellin from S. Typhimurium can induce cell death and cytokine secretion, with NLRP3 and NAIP/NLRC4 playing redundant roles in inflammasome activation during infection.
JOURNAL OF IMMUNOLOGY
(2021)
Article
Multidisciplinary Sciences
Wataru Matsunaga, Toru Shinoe, Moritoshi Hirono
Summary: GAD65-KO mice are more sensitive to the effect of acute ethanol exposure on motor coordination and cerebellar Purkinje cell firing, which may be related to their low GABA concentration in the brain.
Article
Cell Biology
Wulf Tonnus, Francesca Maremonti, Alexia Belavgeni, Markus Latk, Anne Brucker, Anne von Maessenhausen, Claudia Meyer, Sophie Locke, Florian Gembardt, Kristina Beer, Paul Hoppenz, Christian Hugo, Hans-Joachim Anders, Stefan Bornstein, Feng Shao, Andreas Linkermann, Yoshihiro Kusunoki, Jan U. Becker
Summary: This study discovered the protective role of GSDMD in regulating necrosis and alleviating acute kidney injury.
CELL DEATH & DISEASE
(2022)
Article
Immunology
Sophia Hung, Amelie Kasperkowitz, Florian Kurz, Liane Dreher, Joachim Diessner, Eslam S. S. Ibrahim, Stefan Schwarz, Knut Ohlsen, Tobias Hertlein
Summary: Humanized mice have shown increased vulnerability to Staphylococcus aureus infection compared to wild type mice, and this study found that next-generation humanized mice with improved myeloid reconstitution were even more susceptible. The severity of infection was correlated with the rate of humanization. These findings have implications for therapy approaches and analysis of virulence mechanisms.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Pharmacology & Pharmacy
Andre Felipe Rodrigues, Mihail Todiras, Fatimunnisa Qadri, Natalia Alenina, Michael Bader
Summary: The study found that FVB/N mice without angiotensin peptides do not experience hypotension but regulate blood pressure through compensatory mechanisms. However, these mice also exhibit renal morphological and physiological changes, which may make them a model for drug-resistant hypertension.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Immunology
Maria Luisa Barcena, Maximilian H. Niehues, Celine Christiansen, Misael Estepa, Natalie Haritonow, Amir H. Sadighi, Ursula Mueller-Werdan, Yury Ladilov, Vera Regitz-Zagrosek
Summary: The study found that in an inflammatory environment, male mice exhibited stronger polarization and activation of macrophages and cardiac fibroblasts compared to females, suggesting a significant role of sex in cardiac pathologies.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Immunology
Jhansi L. Leslie, Erin Weddle, Lauren K. Yum, Ye Lin, Matthew L. Jenior, Benjamin Lee, Jennie Z. Ma, Beth D. Kirkpatrick, Uma Nayak, James A. Platts-Mills, Herve F. Agaisse, Rashidul Haque, William A. Petri
Summary: The study revealed that infants lacking the Lewis histo-blood group antigen are more susceptible to shigellosis. Inhibition of fucosylation in epithelial cells in vitro was found to decrease invasion by Shigella flexneri, indicating a role for fucosylated glycans in susceptibility to shigellosis.
CLINICAL INFECTIOUS DISEASES
(2021)
Article
Biology
Justin L. Roncaioli, Janet Peace Babirye, Roberto A. Chavez, Fitty L. Liu, Elizabeth A. Turcotte, Angus Y. Lee, Cammie F. Lesser, Russell E. Vance, Arturo Casadevall
Summary: Bacteria of the genus Shigella, which cause shigellosis, can colonize colonic intestinal epithelial cells and result in severe gastrointestinal disease. In this study, the researchers investigate the protective role of cell death pathways during oral Shigella infection in mice. They find that the Caspase-11 inflammasome and TNF alpha, a cytokine that activates Caspase-8-dependent apoptosis, provide protection against Shigella colonization in the absence of the NAIP-NLRC4 pathway. However, the protection is limited when Shigella expresses OspC3, which antagonizes Caspase-11 activity. Overall, the study reveals a layered hierarchy of cell death pathways that limit the ability of Shigella to cause disease.
Article
Immunology
Qian Li, Shuang Li, Yiwei Yao, Zhongxiang Ma, Chutian Huang
Summary: Maternal immune activation during pregnancy affects the development of the nervous system and increases susceptibility to gastrointestinal disorders. This study found that mice with maternal immune activation were more prone to colitis and exhibited elevated macrophage infiltration and cytokine production in the colon. The researchers also discovered defects in the innervation of mucosal sensory nerves and reduced levels of calcitonin gene-related peptide (CGRP) in the colon of these mice. Treatment with recombinant CGRP reversed the hyperinflammatory pathology in the mice, suggesting that CGRP deficiency contributes to their susceptibility to colitis.
BRAIN BEHAVIOR AND IMMUNITY
(2023)
Article
Neurosciences
Eduard Bentea, Laura De Pauw, Lise Verbruggen, Lila C. Winfrey, Lauren Deneyer, Cynthia Moore, Giulia Albertini, Hideyo Sato, Ann Van Eeckhaut, Charles K. Meshul, Ann Massie
Summary: Our study revealed age-related protection against proteasome inhibition-induced nigrostriatal degeneration in xCT(-/-) mice, while xCT deletion failed to protect nigral dopaminergic neurons of aged mice against MPTP-induced toxicity. This provides new insights into the role of system x(c)(-) in mechanisms of dopaminergic cell loss and its interaction with aging.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Xinlei Sun, Fujie Shi, Weiran Wang, Yunfei Wu, Shuang Qu, Jing Li, Hongwei Liang, Ke Zen
Summary: Infiltration of polymorphonuclear neutrophils (PMNs) is critical in acute lung injury (ALI). This study reveals that pyruvate kinase type M2 (PKM2) plays a crucial role in PMN inflammatory responses, and deletion of PKM2 in PMNs impairs their function but protects against LPS-induced ALI.
Article
Virology
Ravi Kant, Lauri Kareinen, Teemu Smura, Tobias L. Freitag, Sawan Kumar Jha, Kari Alitalo, Seppo Meri, Tarja Sironen, Kalle Saksela, Tomas Strandin, Anja Kipar, Olli Vapalahti
Summary: Common laboratory mice are not susceptible to wild-type SARS-CoV-2, but can be infected with mouse-adapted virus strains that contain key mutations similar to those found in naturally occurring variants of concern. The SARS-CoV-2 beta variant was shown to be infectious to BALB/c mice, causing pulmonary changes within 2-3 days post infection, indicating that these mice could serve as a suitable model for evaluating COVID-19 countermeasures.
Article
Immunology
Yajing Gao, Krystin Deason, Aakanksha Jain, Ricardo A. Irizarry-Caro, Igor Dozmorov, Laura A. Coughlin, Isabella Rauch, Bret M. Evers, Andrew Y. Koh, Edward K. Wakeland, Chandrashekhar Pasare
JOURNAL OF EXPERIMENTAL MEDICINE
(2020)
Article
Microbiology
Thomas P. Burke, Patrik Engstrom, Roberto A. Chavez, Joshua A. Fonbuena, Russell E. Vance, Matthew D. Welch
NATURE MICROBIOLOGY
(2020)
Article
Immunology
Jeannette L. Tenthorey, Roberto A. Chavez, Thornton W. Thompson, Katherine A. Deets, Russell E. Vance, Isabella Rauch
JOURNAL OF EXPERIMENTAL MEDICINE
(2020)
Review
Biochemistry & Molecular Biology
Renate Bauer, Isabella Rauch
MOLECULAR ASPECTS OF MEDICINE
(2020)
Article
Neurosciences
Hsiu-Chun Chuang, Eva K. Nichols, Isabella Rauch, Wei-Cheng Chang, Patrick M. Lin, Rhea Misra, Maiko Kitaoka, Russell E. Vance, Kaoru Saijo
Summary: The study demonstrates that mice deficient in inflammasome regulators exhibit abnormal behaviors, and the expression of Casp1 in microglia is essential for preventing these behaviors. Research shows that lytic cell death in microglial cells during embryonic development is crucial for proper neuronal development.
Review
Immunology
Katherine A. Deets, Russell E. Vance
Summary: Recent research highlights the complex relationship between inflammasomes and adaptive immunity, focusing on how inflammasome activation influences the release of cytokines and antigens, shaping or inhibiting adaptive immune responses. Different tissue or cellular contexts may alter the effects of inflammasome activation on adaptive immunity, contributing to beneficial or detrimental outcomes in infectious diseases, cancer, and autoimmunity. The discussion by Deets and Vance explores the impact of inflammasome activation on adaptive immunity.
Article
Immunology
Oyebola O. Oyesola, Michael T. Shanahan, Matt Kanke, Bridget M. Mooney, Lauren M. Webb, Shuchi Smita, Macy K. Matheson, Pamela Campioli, Duc Pham, Simon P. Fruh, John W. McGinty, Madeline J. Churchill, Jordan L. Cahoon, Pavithra Sundaravaradan, Becca A. Flitter, Karthik Mouli, Marija S. Nadjsombati, Elena Kamynina, Seth A. Peng, Rebecca L. Cubitt, Karsten Gronert, James D. Lord, Isabella Rauch, Jakob von Moltke, Praveen Sethupathy, Elia D. Tait Wojno
Summary: The PGD2-CRTH2 pathway negatively regulates the epithelial program during helminth infection, controlling worm clearance and intestinal goblet cell hyperplasia, revealing a mechanism to suppress the inflammatory effects of Type 2 cytokine response.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Review
Immunology
David A. Constant, Timothy J. Nice, Isabella Rauch
Summary: Epithelial cells in barrier tissues play a critical role in immune function by detecting, restricting, and eliminating pathogens. They also detect commensal and dietary products to maintain homeostasis. Recent studies have emphasized the importance of epithelial cells in promoting immune responses and maintaining balance in the body.
CURRENT OPINION IN IMMUNOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Madeline J. Churchill, Patrick S. Mitchell, Isabella Rauch
Summary: Pyroptosis is a form of cell death executed by GSDMs proteins, which release cytokines and eliminate pathogen replication to play a role in host defense. Pyroptosis also occurs in barrier epithelia, but requires unique mechanisms to maintain barrier integrity.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Moritz M. Gaidt, Alyssa Morrow, Marian R. Fairgrieve, Jonathan P. Karr, Nir Yosef, Russell E. Vance
Summary: Pathogens disrupt host immune pathways using virulence factors, triggering a secondary immune response. Human monocytes possess a "self-guarded" immune pathway that does not rely on canonical immune pathways to induce anti-viral interferon. Loss of the target MORC3, a negative regulator of interferon, results in an IRF3- and IRF7-independent interferon response induced by ICP0, a virulence factor of herpes simplex virus type 1.
Article
Multidisciplinary Sciences
Corinne Clave, Witold Dyrka, Elizabeth A. Turcotte, Alexandra Granger-Farbos, Lea Ibaelosa, Benoit Pinson, Russell E. Vance, Sven J. Saupe, Asen Daskalov
Summary: Gasdermins are a family of proteins that control cell death reactions in both mammals and fungi. This study reveals the proteolytic regulation of Gasdermins in fungi, showing an evolutionary parallel between fungal and mammalian cell death pathways.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Biology
Katherine A. Deets, Randilea Nichols Doyle, Isabella Rauch, Russell E. Vance
Summary: The study demonstrates that activation of inflammasomes in intestinal epithelial cells can initiate adaptive immune responses by activating CD8(+) T cells. However, cross-presentation of IEC-derived antigens to CD8(+) T cells is not solely dependent on IEC pyroptosis.
Article
Biology
Justin L. Roncaioli, Janet Peace Babirye, Roberto A. Chavez, Fitty L. Liu, Elizabeth A. Turcotte, Angus Y. Lee, Cammie F. Lesser, Russell E. Vance, Arturo Casadevall
Summary: Bacteria of the genus Shigella, which cause shigellosis, can colonize colonic intestinal epithelial cells and result in severe gastrointestinal disease. In this study, the researchers investigate the protective role of cell death pathways during oral Shigella infection in mice. They find that the Caspase-11 inflammasome and TNF alpha, a cytokine that activates Caspase-8-dependent apoptosis, provide protection against Shigella colonization in the absence of the NAIP-NLRC4 pathway. However, the protection is limited when Shigella expresses OspC3, which antagonizes Caspase-11 activity. Overall, the study reveals a layered hierarchy of cell death pathways that limit the ability of Shigella to cause disease.