Interplay between NOD1 and TLR4 Receptors in Macrophages: Nonsynergistic Activation of Signaling Pathways Results in Synergistic Induction of Proinflammatory Gene Expression.

Interactions between pattern-recognition receptors shape innate immune responses to pathogens. NOD1 and TLR4 are synergistically interacting receptors playing a pivotal role in the recognition of Gram-negative bacteria. However, mechanisms of their cooperation are poorly understood.

Glycolytic reprogramming of macrophages activated by NOD1 and TLR4 agonists: No association with proinflammatory cytokine production in normoxia.

Upon activation with pathogen-associated molecular patterns, metabolism of macrophages and dendritic cells is shifted from oxidative phosphorylation to aerobic glycolysis, which is considered important for proinflammatory cytokine production. Fragments of bacterial peptidoglycan (muramyl peptides) activate innate immune cells through nucleotide-binding oligomerization domain (NOD) 1 and/or NOD2 receptors. Here, we show that NOD1 and NOD2 agonists induce early glycolytic reprogramming of human monocyte-derived macrophages (MDM), which is similar to that induced by the Toll-like receptor 4 (TLR4) agonist lipopolysaccharide.

Synergistic interactions between NOD receptors and TLRs: Mechanisms and clinical implications.

Interactions between pattern recognition receptors (PRRs) shape innate immune responses to particular classes of pathogens. Here, we review interactions between TLRs and nucleotide-binding oligomerization domain 1 and 2 (NOD1 and NOD2) receptors, two major groups of PRRs involved in innate recognition of bacteria. Most of experimental data both in vitro and in vivo suggest that NODs and TLRs synergize with each other at inducing the production of cytokines and antimicrobial peptides.

[The dependence of Toll-receptor expression on pathomorphological features of nasal polyps in patients with polypous rhinosinusitis].

This work was designed to study expression of Toll 1-10 receptors on the surface of cells present in inflammatory infiltrate from nasal polyps and peripheral blood of the patients with polypous rhinosinusitis. It was shown that the intensity of expression depended on the pathomorphological characteristics of nasal polyps. Tissues removed from the patients with polyps of the oedematous type contained more Toll-10 positive cells and showed enhanced expression of Toll-5 receptors on monocytes and lymphocytes, Toll-3 receptors on monocytes, granulocytes, and lymphocytes, and Toll-9 receptors on granulocytes.

[The relationship between eosinophilia and parameters of systemic and local adaptive immunity in patients with polypous rhinosinusitis].

Results of the study on adaptive immunity in patients with polypous rhinosinusitis (PRS) proved to depend on the degree of eosinophilia in the peripheral blood. The patients were allocated to two groups, one comprised of those having up to 150 eosinophils per 1 microliter the other of the patients with a higher eosinophil concentration. Patients of the former group had a significantly reduced number of CD3+, CD4+, CD8+, and CD20+cells in the peripheral blood that may indicate the necessity of administering immunotropic agents.

Evaluation of bactericidal activity of human biological fluids by flow cytofluorimetry.

The ability of biological fluids to kill microbes is an important feature of the human immune system. Following incubation of fluorescein isothiocyanate-labeled Staphylococcus aureus with biological specimens and subsequent staining with propidium iodide, the proportions of killed bacteria were estimated by flow cytometry. FACScan is a simple, quick and reliable method to evaluate bactericidal activity of biological fluids.

Neutrophil activity in chronic granulomatous disease.

The killing of microorganisms by neutrophils causes degranulation of azurophilic, specific, and gelatinase granules into the formed phagolysosomes. During the degranulation process, increased surface expression of CD63 (localized in the azurophilic granules of resting neutrophils) and CD66b/CD67 (from specific granules) can be detected. This results from the fusion of the granule membrane, containing these markers, with a plasma membrane.

[Assessment of bactericidal and growth-inhibiting activity of blood serum using flow cytometry and photometry].

Method of measurement of biological fluids bactericidal activity against Staphylococcus aureus using laser flow cytometry has been developed and proposed for clinical use. Overall bactericidal activity of sera of healthy donors has been assessed by this method. Strong positive correlation between bactericidal activity measured by flow cytometry and ability of the sera of healthy donors to inhibit bacterial growth assessed by photometric method was determined.

[Evaluation of serum bactericidal activity by laser flow cytofluorometry].

A method for evaluation of serum bactericidal activity against S. aureus by laser flow cytofluorometry has been developed and proposed for clinical application. This method was used to study the overall bactericidal activity of donors' sera and to estimate the contribution of complement to the process of bacteriolysis.