Innate Immunity, Stress and Evolution

Natural and trained innate immunity against Mycobacterium tuberculosis

Rigging Innate Immunity against the Flu

Risk of SARS-CoV-2 reinfection and COVID-19 hospitalisation in individuals with natural and hybrid immunity: a retrospective, total population cohort study in Sweden

Background: The inability to evaluate host immunity in a rapid quantitative manner in patients with sepsis has severely hampered development of novel immune therapies. The enzyme-linked immunospot (ELISpot) assay is a functional bioassay that measures the number of cytokine-secreting cells and the relative amount of cytokine produced at the single-cell level. A key advantage of ELISpot is its excellent dynamic range enabling a more precise quantifiable assessment of host immunity. Herein, we tested the hypothesis that the ELISpot assay can detect dynamic changes in both innate and adaptive immunity as they often occur during sepsis. We also tested whether ELISpot could detect the effect of immune drug therapies to modulate innate and adaptive immunity. Methods: Mice were made septic using sublethal cecal ligation and puncture. Blood and spleens were harvested serially, and ex vivo interferon γ and TNF-α production were compared by ELISpot and enzyme-linked immunosorbent assay. The capability of ELISpot to detect changes in innate and adaptive immunity due to in vivo immune therapy with dexamethasone, IL-7, and arginine was also evaluated. Results: ELISpot confirmed a decreased innate and adaptive immunity responsiveness during sepsis progression. More importantly, ELISpot was also able to detect changes in adaptive and innate immunity in response to immune-modulatory reagents, for example, dexamethasone, arginine, and IL-7, in a readily quantifiable manner, as predicted by the reagents known mechanisms of action. ELISpot and enzyme-linked immunosorbent assay results tended to parallel one another although some differences were noted. Conclusion: ELISpot offers a unique capability to assess the functional status of both adaptive and innate immunity over time. The results presented herein demonstrate that ELISpot can also be used to detect and follow the in vivo effects of drugs to ameliorate sepsis-induced immune dysfunction. This capability would be a major advance in guiding new immune therapies in sepsis.

This paper presents a study of the flow of ice in wedge-shaped converging channels. Such flows are encountered in the relatively constricted waters of the Canadian Arctic Archipelago. Ridging, lead opening patterns, development of a highpressure area, and arch formation are some of the processes which take place during ice flow through converging channels. An idealized geometry and steady wind forcing were used in the testing. The results give ice cover velocity, distribution of stresses, ice thickness, area coverage and ridging. Some of the conditions leading to arch formation at the constricted exit of the channel are explored.

Protein overload of proximal tubular cells (PTCs) can promote interstitial injury by unclear mechanisms that may involve activation of innate immunity. We investigated whether prolonged exposure of tubular cells to high protein concentrations stimulates innate immunity, triggering progressive interstitial inflammation and renal injury, and whether specific inhibition of innate or adaptive immunity would provide renoprotection in an established model of massive proteinuria, adriamycin nephropathy (ADR). Adult male Munich–Wistar rats received a single dose of ADR (5 mg/kg, iv), being followed for 2, 4, or 20 weeks. Massive albuminuria was associated with early activation of both the NF-κB and NLRP3 innate immunity pathways, whose intensity correlated strongly with the density of lymphocyte infiltration. In addition, ADR rats exhibited clear signs of renal oxidative stress. Twenty weeks after ADR administration, marked interstitial fibrosis, glomerulosclerosis, and renal functional loss were observed. Administration of mycophenolate mofetil (MMF), 10 mg/kg/day, prevented activation of both innate and adaptive immunity, as well as renal oxidative stress and renal fibrosis. Moreover, MMF treatment was associated with shifting of M from the M1 to the M2 phenotype. In cultivated NRK52-E cells, excess albumin increased the protein content of Toll-like receptor (TLR) 4 (TLR4), NLRP3, MCP-1, IL6, IL-1β, Caspase-1, α-actin, and collagen-1. Silencing of TLR4 and/or NLRP3 mRNA abrogated this proinflammatory/profibrotic behavior. Simultaneous activation of innate and adaptive immunity may be key to the development of renal injury in heavy proteinuric disease. Inhibition of specific components of innate and/or adaptive immunity may be the basis for future strategies to prevent chronic kidney disease (CKD) in this setting.

Foreword: Egesten, A. Schmidt, A. Herwald, H. From Darwin and Metchnikoff to Burnet and Beyond: Cooper, E.L. General Introduction to Innate Immunity: Dr. Jekyl/Mr. Hyde Quality of the Innate Immune System: Zanker, K.S. The Innate Immune System of Mammals and Insects: Muller, U. Vogel, P. Alber, G. Schaub, G.A. Pattern Recognition Receptors and Their Role in Innate Immunity: Focus on Microbial Protein Ligands: Areschoug, T. Gordon, S. Antimicrobial Peptides in Innate Immune Responses: Sorensen, O.E. Borregaard, N. Cole, A.M. Complement: An Efficient Sword of Innate Immunity: Rambach, G. Wurzner, R. Speth, C. Antibacterial Chemokines - Actors in Both Innate and Adaptive Immunity: Eliasson, M. Egesten, A. The Role of Neutrophils and Monocytes in Innate Immunity: Kantari, C. Pederzoli-Ribeil, M. Witko-Sarsat, V. Innate Immune Functions of the Airway Epithelium: Bartlett, J.A. Fischer, A.J. McCray Jr, P.B. Oxidative Innate Immune Defenses by Nox/Duox Family NADPH Oxidases: Rada, B. Leto, T.L. Aging and Impairment of Innate Immunity: Nomellini, V. Gomez, C.R. Kovacs, E.J. Author Index Subject Index.

Active Uptake of Dendritic Cell-Derived Exovesicles by Epithelial Cells Induces the Release of Inflammatory Mediators through a TNF-α-Mediated Pathway

Innate immunity is an ancient form of host defense that is shared by almost all multicellular organisms (1, 2). However, it is not a redundant defense mechanism, and recent evidence has shown that innate immunity not only provides a first line of antimicrobial host defense, but also has a profound impact on the establishment of adaptive immune responses (1, 3). Upon infection, microorganisms are first recognized by cells of the host innate immune system, such as phagocytic leukocytes, endothelial and mucosal epithelial cells, and professional antigen-presenting cells. Recognition of pathogens is primarily mediated by a set of germline-encoded molecules on innate immune cells that are referred to as pattern recognition receptors (PRRs) (3). Well characterized PRRs include CD14, β2-integrins (CD11/CD18), C-type lectins, macrophage scavenger receptors, and complement receptors (CR1/CD35, CR2/CD21) (3). These PRRs are expressed as either membrane-bound or soluble proteins that recognize invariant molecular structures called pathogen-associated molecular patterns (PAMPs) that are shared by many pathogens but not expressed by hosts (3). Examples of PAMPs include LPS, bacterial lipoprotein (BLP), peptidoglycan (PGN) lipoteichoic acid (LTA), unmethylated CpG DNA of bacteria, lipoarabinomannan (LAM) of mycobacteria, and mannans of yeast (3). Recognition of PAMPs by PRRs results in the activation of different intracellular signaling cascades that in turn lead to the expression of various effector molecules (3). One group of effector molecules consists of reactive oxygen and nitrogen intermediates and various antimicrobial peptides that have direct microbicidal activity and collectively provide immediate protection for hosts. Another group includes cytokines, chemokines, adhesion molecules, and acute phase proteins that are involved in inflammation and early host defense as well as the development of adaptive immune responses. The third group consists of the costimulatory molecules B7.1 and B7.2, which bind CD28 on T cells and act as the second signal for T-cell activation. Therefore, signaling by the PRRs helps to bridge innate and adaptive immunity and allows the host to cope more efficiently with microbial infection. In keeping with the important role that innate immunity plays in protecting multicellular organisms from infection, components of the innate immune response, including pathogen recognition molecules, signal transduction pathways, and downstream effector molecules, are all evolutionarily conserved and are used by insects, plants, and mammals (2). Recent studies on the recognition of microbial PAMPs have highlighted the critical role of one group of PRRs, the Toll-like receptors (TLRs), in pathogen recognition and host defense. These TLRs are distinguished from other PRRs by their ability to recognize and, more significantly, discriminate between, different classes of pathogens (reviewed in refs. 4, 5). Engagement of TLRs by pathogens leads to the activation of innate immune responses (5), and a major signaling target of the TLRs is activation of the transcription factor NF-κB, a key regulator of immune and inflammatory responses (reviewed in refs. 6–8). Interestingly, TLR-mediated NF-κB activation is also an evolutionarily conserved event that occurs in phylogenetically distinct species ranging from insects to mammals (5, 9, 10). Here, we focus on the role of the conserved TLR/NF-κB signaling pathway in innate immunity, as well as its impact on adaptive immune responses.

Phagosomes are critical compartments for innate immunity. However, their role in the protection against murine listeriosis has not been examined. We describe here that listericidal phago-receptosomes are induced by the function of IFN-γ or IL-6 as centralized compartments for innate and adaptive immunity because they are able to confer protection against murine listeriosis. These phago-receptosomes elicited LLO(91-99)/CD8(+)- and LLO(189-201)/CD4(+)-specific immune responses and recruited mature dendritic cells to the vaccination sites controlled by T cells. Moreover, they present exceptional features as efficient vaccine vectors. First, they compartmentalize a novel listericidal STAT-1-mediated signaling pathway that confines multiple innate immune components to the same environment. Second, they show features of MHC class II antigen-loading competent compartments for cathepsin-D-mediated LLO processing. Third, murine cathepsin-D deficiencies fail to develop protective immunity after vaccination with listericidal phago-receptosomes induced by IFN-γ or IL-6. Therefore, it appears that the connection of STAT-1 and cathepsin-D in a single compartment is relevant for protection against listeriosis.

Interferon-stimulated genes and their role in controlling hepatitis C virus

How are airborne allergens remembered by the immune system?

Table of Contents 1. Evolutionary Emergence and Interactions among Elements of the Innate and Combinatorial Responses, John J. Marchalonis, G. Kerr Whitfield, and Samuel F. Schluter 2. Drosophila Responses to Microbial Infection: an Overview, Jules A. Hoffman and Petros Ligoxygakis Mammalian Cells 3. Neutrophils: the Power Within, Taco W. Kujipers and Dirk Roos 4. The Biology of Macrophages, R. Tedjo Sasmono and David A. Hume 5. The Regulatory Role of Dendritic Cells in the Innate Immune Response, F. Granucci, S. Feau, I. Zanoni, G. Raimondi, N. Pavelka, C. Vizzardelli, and P. Ricciardi-Castagnoli 6. Roles of Mast Cells and Basophils in Innate Immunity, Stephen J. Galli, Devavani Chatterjea, and Mindy Tsai 7. Innate Natural Killer Cell Responses to Infection, Wayne M. Yokoyama 8. Urinary Tract Infection as a Model for Innate Mucosal Immunity, M. Samuelsson, G. Bergsten, H. Fischer, D. Karpman, I. Leijonhufvud, A.C. Lundstedt, P. Samuelsson, M.L. Svensson, B. Wullt, and C. Svanborg 9. Paneth Cells in Innate Immunity and Intestinal Inflammation, Satish Keshav Humoral Factors 10. Collectins and the Acute-Phase Response, Howard Clark, Thilo Stehle, Alan Ezekowitz, and Kenneth Reid 11. Complement and Its Receptors in Infection, Admar Verschoor and Michael C. Carroll 12. Coagulation and Innate Immunity, Charles T. Esmon Receptors 13. Toll-Like Receptors: Ligands and Signaling, Kiyoshi Takeda and Shizuo Akira 14. Toll-Like Receptors and Control of Adaptive Immunity, Gregory M. Barton, Chandrasheklar Pesare, and Ruslan Medzhitov 15. Antigen-Presenting Cell Receptors and Innate Immunity: Diversity, Recognition, and Responses, Siamon Gordon 16. The Function of Leukocyte Immunoglobulin-Like Receptors in Self-Tolerance, Viral Recognition, and Regulation of Adaptive Responses, Marco Colonna, and Winfried Barchet Effector Responses 17. Antimicrobial Peptides: Effectors of Innate Immunity, Michael Zasloff 18. Antimicrobial Proteins, Tomas Ganz and Robert I. Lehrer 19. Reactive Oxygen and Reactive Nitrogen Metabolites as Effector Molecules Against Infectious Pathogens, Christian Bogdan 20. Chemokines, Bernhard Moser 21. Lipids, K. Frank Austen and Yoshihide Kanaoka 22. Role of Innate Immunity in Microbial Infection, Peter Seiler, Ulrich Steinhoff, and Stephen H.E. Kaufmann

Combining Innate Immunity With Radiation Therapy for Cancer Treatment

Beyond sensing: Retinoic acid inducible gene-I (RIG-I) continues to expand its antiviral effector functions.