Review
Immunology
Cassio Luiz Coutinho Almeida-da-Silva, Luiz Eduardo Baggio Savio, Robson Coutinho-Silva, David M. Ojcius
Summary: The innate immune system in vertebrates and invertebrates relies on conserved receptors and ligands, and pathways to initiate a rapid response against microbial infections and other sources of stress and danger. Research on NOD-like receptors (NLRs) has advanced in the past two decades, providing insight into the ligands and conditions that activate NLRs, as well as the outcomes of NLR activation in cells and animals. NLRs play crucial roles in diverse functions, such as transcription of MHC molecules and initiation of inflammation, and their activation can be direct or indirect depending on the ligands involved. Future discoveries will contribute to a better understanding of the molecular details and physiological consequences of NLR activation.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Critical Care Medicine
Valerie E. Polcz, Jaimar C. Rincon, Russell B. Hawkins, Evan L. Barrios, Philip A. Efron, Lyle L. Moldawer, Shawn D. Larson
Summary: Sepsis is a major cause of neonatal mortality worldwide, and understanding the perinatal immune system is crucial for improving therapies for neonates at risk. This narrative outlines the known and unknown aspects of the human immune system during the immune tolerant phase in utero and the rapidly changing antigen-rich period after birth. The unique immune phenotype in early life contributes to the heightened risk of infection and dysregulated immune responses to external antigens. We discuss the concept of innate immune memory and potential immune modulators to improve resilience to sepsis in newborns.
Article
Fisheries
Chongyang Li, Kui Zhang, Guangzhao Pan, Lei Zhang, Xin Hu, Gaichao Zhao, Chaowei Deng, Mengqin Tan, Changhong Li, Man Xu, Jingjing Su, Li Shen, Saima Kausar, Liqun Yang, Muhammad Nadeem Abbas, Hongjuan Cui
Summary: In this study, the full-length cDNA sequence of Bmintegrin beta 1 was obtained from silkworm. The gene was found to be ubiquitously expressed in different tissues and organs, with highest expression in fat body and hemocytes. Bmintegrin beta 1 may play a role in pathogen agglutination and provides novel insights into its immune functions.
DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY
(2021)
Article
Plant Sciences
Qian Yang, Zhongping Peng, Wenna Ma, Siqi Zhang, Suyin Hou, Jian Wei, Shuwei Dong, Xuya Yu, Yuzhu Song, Wei Gao, Zed Rengel, Luqi Huang, Xiuming Cui, Qi Chen
Summary: The study demonstrates that melatonin plays a significant role in priming stomatal immunity in plants, by regulating stomatal closure and activating kinases to prevent bacterial invasion. The phytomelatonin receptor 1 (PMTR1) is essential for perceiving melatonin signals for stomatal closure and kinase activation in a G alpha subunit GPA1-independent manner.
Article
Microbiology
Stephen A. Klotz, Nicole Bradley, Peter N. Lipke
Summary: The interactions between Candida and macrophages play a crucial role in the immune defense against disseminated and deep-seated candidiasis. This study reveals the significance of the interaction between serum amyloid P-component (SAP) and functional amyloids on Candida cells. Blocking the binding between SAP and macrophages enhances phagocytosis of yeast cells, while promoting amyloid formation on the yeast cell surface also increases phagocytosis by macrophages. Additionally, the use of miridesap, a small palindrome molecule, shows potential in boosting phagocytosis by preventing SAP binding to yeasts and removing bound SAP. These interventions have the potential to enhance the host immune response to disseminated candidiasis.
Review
Pediatrics
Tamara Sljivancanin Jakovljevic, Jelena Martic, Jelena Jacimovic, Nadja Nikolic, Jelena Milasin, Tanja Lazic Mitrovic
Summary: This meta-analysis investigated the association between polymorphisms in genes responsible for innate immunity and neonatal sepsis development. The results suggest that the MBL exon 1 and TLR4 rs4986791 polymorphisms may be associated with the risk of culture-proven sepsis.
WORLD JOURNAL OF PEDIATRICS
(2022)
Review
Immunology
Kai Pohl, Ian A. Cockburn
Summary: Malaria causes hundreds of thousands of deaths annually, but these deaths represent only a small fraction of total malaria cases. Immunity to the causative agent, Plasmodium, is incomplete, but immunization with attenuated parasites can provide complete immunity. The innate immune response plays a crucial role in different stages of the parasite lifecycle, balancing strong proinflammatory responses with regulatory mechanisms to protect the host from life-threatening cytokine storms.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Anna Sophie Heinemann, Jan Lennart Stalp, Joao Pedro Pereira Bonifacio, Filo Silva, Maike Willers, Julia Heckmann, Beate Fehlhaber, Lena Voellger, Dina Raafat, Nicole Normann, Andreas Klos, Gesine Hansen, Mirco Schmolke, Dorothee Viemann
Summary: Infections with influenza A viruses (IAV) cause seasonal epidemics and global pandemics. Silent neonatal influenza infections have a remote beneficial impact on the later control of unrelated pathogen infections. This effect is mediated by improved pathogen clearance and enhanced antimicrobial functions of the innate immune system.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Immunology
Umeharu Ohto
Summary: Innate immunity is a crucial defense mechanism against microbial infections. Innate immune pattern recognition receptors (PRRs) play significant roles in detecting invading pathogens and activating the immune response. Cellular components and pathogen-associated molecular patterns (PAMPs) can trigger inflammatory responses and activate the immune system. Nucleotide-binding and oligomerization domain (NOD)-like receptors (NLRs) constitute a major family of intracellular PRRs and are involved in various diseases.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Yi-Nan Zhang, Jennifer Paynter, Cindy Sou, Tatiana Fourfouris, Ying Wang, Ciril Abraham, Timothy Ngo, Yi Zhang, Linling He, Jiang Zhu
Summary: It was demonstrated that self-assembling protein nanoparticles can effectively neutralize various emerging variants of SARS-CoV-2, which is crucial for enhancing vaccine-induced immunity. The impact of adjuvants on vaccine-induced immunity and the isolation of monoclonal antibodies were studied through various formulations and single-cell sorting. Experimental results showed that the 13-01 v9 SApNP exhibited stronger immune responses compared to soluble spikes, with increased retention, presentation on follicular dendritic cells, and germinal center reactions.
Article
Immunology
Angela Holder, Jeannine Kolakowski, Chloe Rosentreter, Ellen Knuepfer, Sabine A. F. Jegouzo, Oliver Rosenwasser, Heather Harris, Lotta Baumgaertel, Amanda Gibson, Dirk Werling
Summary: Innate immune receptors form complexes with secondary receptors to activate multiple signaling pathways, regulating homeostasis and immunity. A bovine homologue of Mincle (boMincle) has been characterized to be structurally and functionally similar to the human orthologue (huMincle), although there are some differences. BoMincle is predominantly expressed by myeloid cells, but mRNA transcripts were also detected in granulocytes, B cells, and T cells. BoMincle has the potential to recognize endogenous ligands, suggesting its role in homeostasis in cattle.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Jean-Yves Dube, Fiona McIntosh, Marcel A. Behr
Summary: Pattern recognition receptors Mincle and NOD2 are associated with mycobacterial immunity, but single gene knockout studies have shown mild phenotypes. Researchers hypothesized that dual knockout of Mincle and Nod2 would result in a more severe immune phenotype, but the results showed no further effect compared to Nod2 knockout alone.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Diana Talipova, Aiganym Smagulova, Dimitri Poddighe
Summary: This review discusses the potential role of Toll-like receptors (TLRs) in the immunopathogenesis of CD. Although evidence from basic research is limited, differences in TLR expression and activation have been observed between active CD patients and controls or treated CD patients in some clinical studies. Therefore, TLRs may be part of the non-HLA-related genetic factors implicated in CD pathogenesis, considering their potential role in the interaction between the host immune system and environmental factors.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Immunology
Poornima Sankar, Bibhuti Bhusan Mishra
Summary: Tuberculosis remains a global health challenge, causing a significant number of deaths every year. The interaction between Mycobacterium tuberculosis and innate immune cells, such as macrophages and dendritic cells, plays a crucial role in the host defense against the infection. However, our understanding of these interactions is still limited. This review focuses on exploring the early host-pathogen interactions and the contribution of various innate immune cells and mucosal barrier in tuberculosis immunity.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Immunology
Andrew Snyder, Kathleen Jedreski, James Fitch, Saranga Wijeratne, Amy Wetzel, Josey Hensley, Margaret Flowers, Katherine Bline, Mark W. Hall, Jennifer A. Muszynski
Summary: This study investigated RNA expression patterns in children with septic shock and found differences in key pathways between those with immunoparalysis and normal immune response. Downregulated pathways in immunoparalyzed children involved interactions between innate and adaptive immune cells, while upregulated pathways included humoral immunity and platelet activation. This research suggests potential for gene expression data to identify immunoparalysis in children and highlights key pathways in both innate and adaptive immunity that are differentially regulated.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Critical Care Medicine
Scott C. Brakenridge, Zhongkai Wang, Michael Cox, Steven Raymond, Russell Hawkins, Dijoia Darden, Gabriela Ghita, Babette Brumback, Joseph Cuschieri, Ronald Maier, Frederick A. Moore, Alicia M. Mohr, Philip A. Efron, Lyle L. Moldawer
Summary: A study identified three distinct immunologic endotypes after severe injury, each with unique associations to different clinical trajectories. Endotype iA showed a moderate initial proinflammatory response and primarily led to rapid recovery, while endotype iB and iC exhibited different inflammatory response patterns, with iB associated with chronic critical illness and poor outcomes.
JOURNAL OF TRAUMA AND ACUTE CARE SURGERY
(2021)
Article
Medicine, Research & Experimental
Tianmeng Chen, Matthew J. Delano, Kong Chen, Jason L. Sperry, Rami A. Namas, Ashley J. Lamparello, Meihong Deng, Julia Conroy, Lyle L. Moldawer, Philip A. Efron, Patricia Loughran, Christopher Seymour, Derek C. Angus, Yoram Vodovotz, Wei Chen, Timothy R. Billiar
Summary: The immune response after trauma was investigated using single-cell RNA sequencing, revealing significant changes in gene expression in monocytes in both mice and humans. Human CD14(+) monocytes were classified into 6 signatures, defining two subtypes of trauma patients with differences in recovery, organ dysfunction, and complications. These subtypes were also observed in burn and sepsis patients, indicating a shared immune response pattern in critical illness.
Article
Pediatrics
Irina Prelipcean, James Lawrence Wynn, Lindsay Thompson, David James Burchfield, Laurence James-Woodley, Philip B. Chase, Christopher P. Barnes, Angelina Bernier
Summary: This study examined the relationship between cortisol concentrations and illness severity in extremely preterm infants, finding no significant correlation between the two factors. Further research is needed to identify clinically useful mediators of adrenal dysfunction and guide clinical management.
ARCHIVES OF DISEASE IN CHILDHOOD-FETAL AND NEONATAL EDITION
(2021)
Article
Obstetrics & Gynecology
Khyzer B. Aziz, Orlyn C. Lavilla, James L. Wynn, Allison C. Lure, Daniel Gipson, Diomel de la Cruz
Summary: The study found that the maximum vasoactive-inotropic (VISmax) in extremely premature and extremely low birth weight infants was significantly associated with mortality, serving as an important predictor for risk stratification and neonatal precision medicine.
JOURNAL OF PERINATOLOGY
(2021)
Review
Medicine, General & Internal
Brittany P. Fenner, D. B. Darden, Lauren S. Kelly, Jaimar Rincon, Scott C. Brakenridge, Shawn D. Larson, Frederick A. Moore, Philip A. Efron, Lyle L. Moldawer
Summary: Improved management of severe sepsis has led to a significant reduction in in-hospital mortality, but has also given rise to a new syndrome called chronic critical illness (CCI). CCI affects sepsis survivors who fail to fully recover and progress into a state of manageable organ injury requiring prolonged intensive care. This syndrome is driven by a maladaptive host response to chronic processes, resulting in a persistent inflammatory, immune suppressive and protein catabolic syndrome (PICS). Despite being a common outcome, there are currently no therapeutic interventions other than supportive therapies for PICS, highlighting the need for a better understanding of its underlying immunological endotype to guide the development of effective treatments.
FRONTIERS IN MEDICINE
(2021)
Article
Obstetrics & Gynecology
Angela C. Zeigler, John E. Ainsworth, Karen D. Fairchild, James L. Wynn, Brynne A. Sullivan
Summary: This study analyzed the application of HRC index and nSOFA score in VLBW infants. It found that the HRC index can provide early warning of sepsis, while nSOFA score can better predict mortality.
AMERICAN JOURNAL OF PERINATOLOGY
(2023)
Review
Medicine, General & Internal
Dijoia B. Darden, Lauren S. Kelly, Brittany P. Fenner, Lyle L. Moldawer, Alicia M. Mohr, Philip A. Efron
Summary: Protocolized surveillance, diagnosis, and management of septic patients, especially surgical sepsis patients, can significantly increase the number of patients surviving their initial hospitalization. However, some patients may develop chronic critical illness, with elderly and comorbid patients being particularly susceptible to poor outcomes.
JOURNAL OF CLINICAL MEDICINE
(2021)
Review
Medicine, General & Internal
Grant Barker, Christiaan Leeuwenburgh, Todd Brusko, Lyle Moldawer, Srinivasa T. Reddy, Faheem W. Guirgis
Summary: Lipids and lipoproteins have pleiotropic effects on the innate immune system, undergo important changes during sepsis, and play roles in regulating immune response and inflammation escalation and resolution. Dysfunctional HDL and specialized pro-resolving mediators are key elements in predicting adverse outcomes and influencing the course of inflammation in sepsis. Further research into lipid dysregulation and chronic inflammation during sepsis is essential for risk stratification and personalized therapies.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Immunology
Dijoia B. Darden, Xiaoru Dong, Maigan A. Brusko, Lauren Kelly, Brittany Fenner, Jaimar C. Rincon, Marvin L. Dirain, Ricardo Ungaro, Dina C. Nacionales, Marie Gauthier, Michael Kladde, Todd M. Brusko, Azra Bihorac, Frederick A. Moore, Tyler Loftus, Rhonda Bacher, Lyle L. Moldawer, Alicia M. Mohr, Philip A. Efron
Summary: Late after sepsis, circulating lymphoid cells show a unique transcriptomic pattern reflecting immunosuppression and low-grade inflammation, with differences identified between patients with bacterial and fungal sepsis. This highlights a potential role for precision medicine-guided immunomodulatory therapy in post-sepsis patients with chronic critical illness.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Medicine, General & Internal
Dijoia B. Darden, Gabriela L. Ghita, Zhongkai Wang, Julie A. Stortz, Maria-Cecilia Lopez, Michael C. Cox, Russell B. Hawkins, Jaimar C. Rincon, Lauren S. Kelly, Brittany P. Fenner, Tezcan Ozrazgat-Baslanti, Christiaan Leeuwenburgh, Azra Bihorac, Tyler J. Loftus, Frederick A. Moore, Scott C. Brakenridge, Henry Baker, Rhonda Bacher, Alicia M. Mohr, Lyle L. Moldawer, Philip A. Efron
Summary: The study found that sepsis survivors have unique blood leukocyte transcriptomes in late sepsis, indicating ongoing immune dyscrasia which could help understand the prognosis of sepsis patients with CCI.
JOURNAL OF CLINICAL MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Nicole Prince, Min Kim, Rachel S. Kelly, Joann Diray-Arce, Klaus Bonnelykke, Bo L. Chawes, Mengna Huang, Ofer Levy, Augusto A. Litonjua, Jakob Stokholm, Craig E. Wheelock, Hans Bisgaard, Scott T. Weiss, Jessica A. Lasky-Su
Summary: Recurrent respiratory infections are a major cause of illness and death in early childhood. This study investigates the association between steroid metabolites and infection susceptibility in children. The findings suggest that lower levels of certain steroid metabolites may indicate a higher risk of infections. Further research is needed to evaluate the potential of using steroid metabolite measurement as a screening tool for infection susceptibility during this critical developmental period.
Review
Pharmacology & Pharmacy
Branden Lee, Etsuro Nanishi, Ofer Levy, David J. Dowling
Summary: Infection remains a major cause of illness and death worldwide, particularly among the very young and immunocompromised populations. Precision vaccine discovery and development aims to optimize immunizations across all age groups by studying the differences in immune systems and developing tailored vaccines for vulnerable populations.
Article
Critical Care Medicine
Faheem W. Guirgis, Lauren Page Black, Morgan Henson, Guillaume Labilloy, Carmen Smotherman, Charlotte Hopson, Ian Tfirn, Elizabeth L. DeVos, Christiaan Leeuwenburgh, Lyle Moldawer, Susmita Datta, Todd M. Brusko, Alexis Hester, Andrew Bertrand, Victor Grijalva, Alexander Arango-Esterhay, Frederick A. Moore, Srinivasa T. Reddy
Summary: This study found that lipoproteins can predict poor outcomes in sepsis patients, and identified two distinct phenotypes: the Hypolipoprotein phenotype with lower lipoprotein levels and worse clinical outcomes, and the Normolipoprotein cluster with better outcomes.
Letter
Critical Care Medicine
Lyle L. Moldawer, Dijoia B. Darden, Philip A. Efron
Article
Critical Care Medicine
David Miranda, Rebecca Maine, Mackenzie Cook, Scott Brakenridge, Lyle Moldawer, Saman Arbabi, Grant O'Keefe, Bryce Robinson, Eileen M. Bulger, Ronald Maier, Joseph Cuschieri
Summary: Hypothermia is independently associated with the development of CCI in severely injured patients. Transcriptomic analysis revealed unique genomic changes in circulating monocytes of hypothermic patients, indicating a potential link between hypothermia-induced changes and persistent CCI.
TRAUMA SURGERY & ACUTE CARE OPEN
(2021)