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Julio Silva, Takehiro Takahashi, Jamie Wood, Peiwen Lu, Alexandra Tabachnikova, Jeff R Gehlhausen, Kerrie Greene, Bornali Bhattacharjee, Valter Silva Monteiro, Carolina Lucas, Rahul M Dhodapkar, Laura Tabacof, Mario Peña-Hernandez, Kathy Kamath, Tianyang Mao, Dayna Mccarthy, Ruslan Medzhitov, David van Dijk, Harlan M Krumholz, Leying Guan, David Putrino, Akiko Iwasaki
Strong sex differences in the frequencies and manifestations of Long COVID (LC) have been reported with females significantly more likely than males to present with LC after acute SARS-CoV-2 infection 1-7 . However, whether immunological traits underlying LC differ between sexes, and whether such differences explain the differential manifestations of LC symptomology is currently unknown. Here, we performed sex-based multi-dimensional immune-endocrine profiling of 165 individuals 8 with and without LC in an exploratory, cross-sectional study to identify key immunological traits underlying biological sex differences in LC...
March 4, 2024: medRxiv
#2
JOURNAL ARTICLE
Jon Klein, Jamie Wood, Jillian Jaycox, Rahul M Dhodapkar, Peiwen Lu, Jeff R Gehlhausen, Alexandra Tabachnikova, Kerrie Greene, Laura Tabacof, Amyn A Malik, Valter Silva Monteiro, Julio Silva, Kathy Kamath, Minlu Zhang, Abhilash Dhal, Isabel M Ott, Gabrielee Valle, Mario Peña-Hernandez, Tianyang Mao, Bornali Bhattacharjee, Takehiro Takahashi, Carolina Lucas, Eric Song, Dayna Mccarthy, Erica Breyman, Jenna Tosto-Mancuso, Yile Dai, Emily Perotti, Koray Akduman, Tiffany J Tzeng, Lan Xu, Anna C Geraghty, Michelle Monje, Inci Yildirim, John Shon, Ruslan Medzhitov, Denyse Lutchmansingh, Jennifer D Possick, Naftali Kaminski, Saad B Omer, Harlan M Krumholz, Leying Guan, Charles S Dela Cruz, David van Dijk, Aaron M Ring, David Putrino, Akiko Iwasaki
Post-acute infection syndromes (PAIS) may develop after acute viral disease1 . Infection with SARS-CoV-2 can result in the development of a PAIS known as "Long COVID" (LC). Individuals with LC frequently report unremitting fatigue, post-exertional malaise, and a variety of cognitive and autonomic dysfunctions2-4 ; however, the biological processes associated with the development and persistence of these symptoms are unclear. Here, 273 individuals with or without LC were enrolled in a cross-sectional study that included multi-dimensional immune phenotyping and unbiased machine learning methods to identify biological features associated with LC...
September 25, 2023: Nature
#3
REVIEW
Miri Adler, Arun R Chavan, Ruslan Medzhitov
Animal tissues are made up of multiple cell types that are increasingly well-characterized, yet our understanding of the core principles that govern tissue organization is still incomplete. This is in part because many observable tissue characteristics, such as cellular composition and spatial patterns, are emergent properties, and as such, they cannot be explained through the knowledge of individual cells alone. Here we propose a complex systems theory perspective to address this fundamental gap in our understanding of tissue biology...
October 16, 2023: Annual Review of Cell and Developmental Biology
#4
JOURNAL ARTICLE
Esther B Florsheim, Nathaniel D Bachtel, Jaime Cullen, Bruna G C Lima, Mahdieh Godazgar, Fernando Carvalho, Carolina P Chatain, Marcelo R Zimmer, Cuiling Zhang, Gregory Gautier, Pierre Launay, Andrew Wang, Marcelo O Dietrich, Ruslan Medzhitov
In addition to its canonical function of protection from pathogens, the immune system can also alter behaviour1,2 . The scope and mechanisms of behavioural modifications by the immune system is not yet well understood. Here, using mouse models of food allergy, we show that allergic sensitization drives antigen-specific avoidance behaviour. Allergen ingestion activates brain areas involved in the response to aversive stimuli, including the nucleus of tractus solitarius, parabrachial nucleus, and central amygdala...
July 12, 2023: Nature
#5
Jon Klein, Jamie Wood, Jillian Jaycox, Peiwen Lu, Rahul M Dhodapkar, Jeff R Gehlhausen, Alexandra Tabachnikova, Laura Tabacof, Amyn A Malik, Kathy Kamath, Kerrie Greene, Valter Silva Monteiro, Mario Peña-Hernandez, Tianyang Mao, Bornali Bhattacharjee, Takehiro Takahashi, Carolina Lucas, Julio Silva, Dayna Mccarthy, Erica Breyman, Jenna Tosto-Mancuso, Yile Dai, Emily Perotti, Koray Akduman, Tiffany J Tzeng, Lan Xu, Inci Yildirim, Harlan M Krumholz, John Shon, Ruslan Medzhitov, Saad B Omer, David van Dijk, Aaron M Ring, David Putrino, Akiko Iwasaki
SARS-CoV-2 infection can result in the development of a constellation of persistent sequelae following acute disease called post-acute sequelae of COVID-19 (PASC) or Long COVID 1-3 . Individuals diagnosed with Long COVID frequently report unremitting fatigue, post-exertional malaise, and a variety of cognitive and autonomic dysfunctions 1-3 ; however, the basic biological mechanisms responsible for these debilitating symptoms are unclear. Here, 215 individuals were included in an exploratory, cross-sectional study to perform multi-dimensional immune phenotyping in conjunction with machine learning methods to identify key immunological features distinguishing Long COVID...
August 10, 2022: medRxiv
#6
JOURNAL ARTICLE
Karen Agaronyan, Lokesh Sharma, Bharat Vaidyanathan, Keith Glenn, Shuang Yu, Charles Annicelli, Talia D Wiggen, Mitchell R Penningroth, Ryan C Hunter, Charles S Dela Cruz, Ruslan Medzhitov
Different effector arms of the immune system are optimized to protect from different classes of pathogens. In some cases, pathogens manipulate the host immune system to promote the wrong type of effector response-a phenomenon known as immune deviation. Typically, immune deviation helps pathogens to avoid destructive immune responses. Here, we report on a type of immune deviation whereby an opportunistic pathogen, Pseudomonas aeruginosa (P. aeruginosa), induces the type 2 immune response resulting in mucin production that is used as an energy source by the pathogen...
May 10, 2022: Immunity
#7
JOURNAL ARTICLE
Carolina Lucas, Patrick Wong, Jon Klein, Tiago B R Castro, Julio Silva, Maria Sundaram, Mallory K Ellingson, Tianyang Mao, Ji Eun Oh, Benjamin Israelow, Takehiro Takahashi, Maria Tokuyama, Peiwen Lu, Arvind Venkataraman, Annsea Park, Subhasis Mohanty, Haowei Wang, Anne L Wyllie, Chantal B F Vogels, Rebecca Earnest, Sarah Lapidus, Isabel M Ott, Adam J Moore, M Catherine Muenker, John B Fournier, Melissa Campbell, Camila D Odio, Arnau Casanovas-Massana, Roy Herbst, Albert C Shaw, Ruslan Medzhitov, Wade L Schulz, Nathan D Grubaugh, Charles Dela Cruz, Shelli Farhadian, Albert I Ko, Saad B Omer, Akiko Iwasaki
Recent studies have provided insights into the pathogenesis of coronavirus disease 2019 (COVID-19)1-4 . However, the longitudinal immunological correlates of disease outcome remain unclear. Here we serially analysed immune responses in 113 patients with moderate or severe COVID-19. Immune profiling revealed an overall increase in innate cell lineages, with a concomitant reduction in T cell number. An early elevation in cytokine levels was associated with worse disease outcomes. Following an early increase in cytokines, patients with moderate COVID-19 displayed a progressive reduction in type 1 (antiviral) and type 3 (antifungal) responses...
August 2020: Nature
#8
REVIEW
Peter Agre, Carolyn Bertozzi, Mina Bissell, Kevin P Campbell, Richard D Cummings, Umesh R Desai, Mary Estes, Terence Flotte, Guy Fogleman, Fred Gage, David Ginsburg, Jeffrey I Gordon, Gerald Hart, Vincent Hascall, Laura Kiessling, Stuart Kornfeld, John Lowe, John Magnani, Lara K Mahal, Ruslan Medzhitov, Richard J Roberts, Robert Sackstein, Rita Sarkar, Ronald Schnaar, Nancy Schwartz, Ajit Varki, David Walt, Irving Weissman
This position statement originated from a working group meeting convened on April 15, 2015, by the NHLBI and incorporates follow-up contributions by the participants as well as other thought leaders subsequently consulted, who together represent research fields relevant to all branches of the NIH. The group was deliberately composed not only of individuals with a current research emphasis in the glycosciences, but also of many experts from other fields, who evinced a strong interest in being involved in the discussions...
February 2016: Journal of Clinical Investigation
#9
JOURNAL ARTICLE
Oscar R Colegio, Ngoc-Quynh Chu, Alison L Szabo, Thach Chu, Anne Marie Rhebergen, Vikram Jairam, Nika Cyrus, Carolyn E Brokowski, Stephanie C Eisenbarth, Gillian M Phillips, Gary W Cline, Andrew J Phillips, Ruslan Medzhitov
Macrophages have an important role in the maintenance of tissue homeostasis. To perform this function, macrophages must have the capacity to monitor the functional states of their 'client cells': namely, the parenchymal cells in the various tissues in which macrophages reside. Tumours exhibit many features of abnormally developed organs, including tissue architecture and cellular composition. Similarly to macrophages in normal tissues and organs, macrophages in tumours (tumour-associated macrophages) perform some key homeostatic functions that allow tumour maintenance and growth...
September 25, 2014: Nature
#10
JOURNAL ARTICLE
Hameeda Sultana, Girish Neelakanta, Harald G Foellmer, Ruth R Montgomery, John F Anderson, Raymond A Koski, Ruslan M Medzhitov, Erol Fikrig
Semaphorin 7A (Sema7A) is a membrane-associated/secreted protein that plays an essential role in connecting the vertebrate neuronal and immune systems. However, the role of Sema7A has not been elucidated in viral pathogenesis. In this study, we show that abrogation of Sema7A protects mice from lethal West Nile virus (WNV) infection. Mice lacking Sema7A showed increased survival, reduced viral burden, and less blood-brain barrier permeability upon WNV infection. Increased Sema7A levels were evident in murine tissues, as well as in murine cortical neurons and primary human macrophages upon WNV infection...
September 15, 2012: Journal of Immunology
#11
Karina R Bortoluci, Ruslan Medzhitov
Cells can die by distinct mechanisms with particular impacts on the immune response. In addition to apoptosis and necrosis, recent studies lead to characterization of a new proinflammatory form of cell death, pyroptosis. TLR and NLR, central innate immune sensors, can control infections by modulating host cell survival. In addition, TLRs can promote the induction of autophagy, thus promoting delivery of infecting pathogens to the lysosomes. On the other hand, activation of some NLR members, especially NLRC4 and NAIP5, leads to the infected cell death by pyroptosis, which is accompanied by secretion of the proinflammatory cytokines IL-1beta, IL-18, and IL-33...
March 24, 2010: Cellular and Molecular Life Sciences: CMLS
#12
REVIEW
Karina R Bortoluci, Ruslan Medzhitov
Cells can die by distinct mechanisms with particular impacts on the immune response. In addition to apoptosis and necrosis, recent studies lead to characterization of a new pro-inflammatory form of cell death, pyroptosis. TLR and NLR, central innate immune sensors, can control infections by modulating host cell survival. In addition, TLRs can promote the induction of autophagy, thus promoting delivery of infecting pathogens to the lysosomes. On the other hand, activation of some NLR members, especially NLRC4 and NAIP5, leads to the infected cell death by pyroptosis, which is accompanied by secretion of the pro-inflammatory cytokines IL-1beta, IL-18, and IL-33...
May 2010: Cellular and Molecular Life Sciences: CMLS
#13
REVIEW
C L Sokol, R Medzhitov
Basophils that were long thought to have a redundant role in mast cells in the effector response to allergens and parasites are now being recognized to have important roles in the regulation of adaptive immune responses. Recent data have revealed their role in the initiation of the T helper cell 2 (Th2)-mediated immune response. Not only do basophils guide the Th1-Th2 balance by providing an early source of crucial Th2-skewing cytokines, interleukin (IL)-4 and thymic stromal lymphopoietin, but recent findings have also illustrated their capacity to function as antigen-presenting cells...
March 2010: Mucosal Immunology
#14
REVIEW
S Rakoff-Nahoum, R Medzhitov
Our studies have focused on understanding the mechanisms of interactions between the indigenous intestinal flora and the mammalian host in both physiological and nonphysiological conditions. In particular, we have focused on the function of innate microbial pattern recognition by Toll-like receptors in the context of tissue injury and repair, spontaneous colitis, and postnatal development.
November 2008: Mucosal Immunology
#15
REVIEW
S Rakoff-Nahoum, R Medzhitov
Toll-like receptors (TLRs) play a critical role in host defense from microbial infection. TLRs recognize conserved molecular structures produced by microorganisms and induce activation of innate and adaptive immune responses. The inflammatory responses induced by TLRs play an important role TLRs not only in host defense from infection, but also in tissue repair and regeneration. This latter function of TLRs can also contribute to tumorigenesis. Here we review recent progress in understanding the role of TLRs in cancer development...
May 2008: Biochemistry. Biokhimii︠a︡
#16
REVIEW
Elin S Mortensen, Kristin A Fenton, Ole P Rekvig
Systemic lupus erythematosus (SLE) is an autoimmune syndrome characterized by autoantibodies to nuclear constituents. Some of these antibodies are diagnostically important, whereas others act as disease-modifying factors. One clinically important factor is autoantibodies against dsDNA and nucleosomes, which have overlapping diagnostic and nephritogenic impact in SLE. Although a scientific focus for 5 decades, the molecular and cellular origin of these antibodies, and why they are associated with lupus nephritis, is still not fully understood...
February 2008: American Journal of Pathology
#17
JOURNAL ARTICLE
David van Duin, Subhasis Mohanty, Venetta Thomas, Sandra Ginter, Ruth R Montgomery, Erol Fikrig, Heather G Allore, Ruslan Medzhitov, Albert C Shaw
The effects of aging on human TLR function remain incompletely understood. We assessed TLR function and expression in peripheral blood monocytes from 159 subjects in 2 age categories, 21-30 and >65 years of age, using a multivariable mixed effect model. Using flow cytometry to assess TLR-induced cytokine production, we observed a substantial, highly significant defect in TLR1/2-induced TNF-alpha (p = 0.0003) and IL-6 (p < 0.0001) production, in older adults compared with young controls. In contrast to findings in aged mice, other TLR (including TLR2/6)-induced cytokine production appeared largely intact...
January 15, 2007: Journal of Immunology
#18
REVIEW
S Rakoff-Nahoum, R Medzhitov
Host organisms live in intimate contact with indigenous microflora. The interactions between the host and commensal microbiota are highly complex and heterogeneous. A growing body of evidence indicates that commensal symbionts provide many benefits to the host physiology, particularly in the gastrointestinal system. The molecular mechanisms of the mutualistic interactions between the host and commensals are largely unknown but can be due either to bioactivity of the commensals or to the reaction of the host immune system to the commensal-derived products...
2006: Current Topics in Microbiology and Immunology
#19
COMPARATIVE STUDY
Dianhua Jiang, Jiurong Liang, Juan Fan, Shuang Yu, Suping Chen, Yi Luo, Glenn D Prestwich, Marcella M Mascarenhas, Hari G Garg, Deborah A Quinn, Robert J Homer, Daniel R Goldstein, Richard Bucala, Patty J Lee, Ruslan Medzhitov, Paul W Noble
Mechanisms that regulate inflammation and repair after acute lung injury are incompletely understood. The extracellular matrix glycosaminoglycan hyaluronan is produced after tissue injury and impaired clearance results in unremitting inflammation. Here we report that hyaluronan degradation products require MyD88 and both Toll-like receptor (TLR)4 and TLR2 in vitro and in vivo to initiate inflammatory responses in acute lung injury. Hyaluronan fragments isolated from serum of individuals with acute lung injury stimulated macrophage chemokine production in a TLR4- and TLR2-dependent manner...
November 2005: Nature Medicine
#20
REVIEW
Salman T Qureshi, R Medzhitov
Effective host defense against microbial infection depends upon prompt recognition of pathogens, activation of immediate containment measures, and ultimately the generation of a specific and definitive adaptive immune response. The innate immune system of the host is responsible for providing constant surveillance against infection; when confronted by pathogens it deploys a series of rapidly acting antimicrobial effectors while simultaneously instructing the adaptive immune system as to the nature and context of the infectious threat...
March 2003: Genes and Immunity
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