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A well-controlled innate immune response is characterized by a rapid yet self-limiting inflammatory response. Although much is known about the range of inflammatory stimuli capable of triggering an innate immune response, the mechanisms which govern the degree of inflammation induced by inflammatory insults and the mechanisms in place to reset or maintain homeostasis are poorly understood. Tumor necrosis factor (TNF) is a potent early response pro-inflammatory cytokine produced by immune cells following a broad range of insults spanning autoimmunity and metabolic diseases to pathogenic infections. Previous studies have shown that a disintegrin and metalloproteinase (ADAM) 17 controls the release of soluble TNF and epidermal growth factor receptor signaling. Utilizing a genetic model of ADAM17 deficiency through the deletion of its regulator, the inactive rhomboid 2 (iRhom2), we show that loss of ADAM17 activity in innate immune cells leads to decreased expression of various cytokines in response to low levels of pathogen-associated molecular pattern (PAMP) stimulation but not at high-dose stimulation. In addition, TNF receptor (TNFR) 1/2-deficient bone marrow-derived macrophages yielded significantly reduced TNF expression following low levels of PAMP stimulation, suggesting that signaling through the TNFRs in immune cells drives a feed-forward regulatory mechanism wherein low levels of TNF allow sustained enhancement of TNF expression in an iRhom2/ADAM17-dependent manner. Thus, we demonstrate that inflammatory expression of TNF and IL1β is differentially regulated following high or low doses of PAMP stimulation, invoking the activation of a previously unknown regulatory mechanism of inflammation.Bacterial and archaeal CRISPR-Cas systems offer adaptive immune protection against foreign mobile genetic elements (MGEs). This function is regulated by sequence specific binding of CRISPR RNA (crRNA) to target DNA/RNA, with an additional requirement of a flanking DNA motif called the protospacer adjacent motif (PAM) in certain CRISPR systems. In this review, we discuss how the same fundamental mechanism of RNA-DNA and/or RNA-RNA complementarity is utilized by bacteria to regulate two distinct functions to ward off intruding genetic materials and to modulate diverse physiological functions. The best documented examples of alternate functions are bacterial virulence, biofilm formation, adherence, programmed cell death, and quorum sensing. While extensive complementarity between the crRNA and the targeted DNA and/or RNA seems to constitute an efficient phage protection system, partial complementarity seems to be the key for several of the characterized alternate functions. Cas proteins are also involved in sequence-specific and non-specific RNA cleavage and control of transcriptional regulator expression, the mechanisms of which are still elusive. Over the past decade, the mechanisms of RNA-guided targeting and auxiliary functions of several Cas proteins have been transformed into powerful gene editing and biotechnological tools. We provide a synopsis of CRISPR technologies in this review. Even with the abundant mechanistic insights and biotechnology tools that are currently available, the discovery of new and diverse CRISPR types holds promise for future technological innovations, which will pave the way for precision genome medicine.Albeit the lungs were thought to be sterile, recent scientific data reported a microbial microbiota in the lungs of healthy individuals. Apparently, new developments in technological approachesincluding genome sequencing methodologies contributed in the identification of the microbiota and shed light on the role of the gut and lung microbiomes in the development of respiratory diseases. Moreover, knowledge of the human microbiome in health may act as a tool for evaluating characteristic shifts in the case of disease. This review paper discusses the development of respiratory disease linked to the intestinal dysbiosis which influences the lung immunity and microbiome. The gastrointestinal-lung dialogue provides interesting aspects in the pathogenesis of the respiratory diseases. Lastly, we were further interested on the role of this interconnection in the progression and physiopathology of newly emergedCOVID-19.Plasmodium sporozoites are transmitted to mammals by anopheline mosquitoes and first infect the liver, where they transform into replicative exoerythrocytic forms, which subsequently release thousands of merozoites that invade erythrocytes and initiate the malaria disease. In some species, sporozoites can transform into dormant hypnozoites in the liver, which cause malaria relapses upon reactivation. Transmission from the insect vector to a mammalian host is a critical step of the parasite life cycle, and requires tightly regulated gene expression. Sporozoites are formed inside oocysts in the mosquito midgut and become fully infectious after colonization of the insect salivary glands, where they remain quiescent until transmission. Parasite maturation into infectious sporozoites is associated with reprogramming of the sporozoite transcriptome and proteome, which depends on multiple layers of transcriptional and post-transcriptional regulatory mechanisms. An emerging scheme is that gene expression in Plasmodium sporozoites is controlled by alternating waves of transcription activity and translational repression, which shape the parasite RNA and protein repertoires for successful transition from the mosquito vector to the mammalian host.Periodic fever, aphthous stomatitis, pharyngitis and adenitis syndrome (PFAPA) is the most common periodic fever syndrome in children with unknown etiology, effectively treated with tonsillectomy. Earlier we have shown that tonsil microbiome is different in patients with PFAPA as compared to that in controls. Recently, fungal microbiome, mycobiome, has been linked to the pathogenesis of inflammatory diseases. We now investigated the role of mycobiome of tonsils in PFAPA. Random forest classification, a machine learning approach, was used for the analysis of mycobiome data. We examined tonsils from 30 children with PFAPA and 22 control children undergoing tonsillectomy for non-infectious reasons. We identified 103 amplicon sequence variants, mainly from two fungal phyla, Ascomycota and Basidiomycota. The mean relative abundance of Candida albicans in the tonsil mycobiome was 11% (95% CI 19 to 27%) in cases and 3.4 % (95% CI -0.8% to 8%) in controls, p =0.104. Mycobiome data showed no statistical difference in differentiating between PFAPA cases and controls compared to a random chance classifier (area under the curve (AUC) = 0.47, SD = 0.05, p = 0.809). In conclusion, in this controlled study, tonsillar mycobiome in children with PFAPA syndrome did not differ from that of the controls.Campylobacter species are Gram-negative, motile, and non-spore-forming bacteria with a unique helical shape that changes to filamentous or coccoid as an adaptive response to environmental stresses. The relatively small genome (1.6 Mbp) of Campylobacter with unique cellular and molecular physiology is only understood to a limited extent. The overall strict requirement of this fastidious microorganism to be either isolated or cultivated in the laboratory settings make itself to appear as a weak survivor and/or an easy target to be inactivated in the surrounding environment of poultry farms, such as soil, water source, dust, surfaces and air. The survival of this obligate microaerobic bacterium from poultry farms to slaughterhouses and the final poultry products indicates that Campylobacter has several adaptive responses and/or environmental niches throughout the poultry production chain. Many of these adaptive responses remain puzzles. No single control method is yet known to fully address Campylobacter contamination in the poultry industry and new intervention strategies are required. The aim of this review article is to discuss the transmission, survival, and adaptation of Campylobacter species in the poultry production environments. Some approved and novel control methods against Campylobacter species throughout the poultry production chain will also be discussed.Bordetella pertussis is a highly contagious pathogen which causes whooping cough in humans. A major pathophysiology of infection is the extrusion of ciliated cells and subsequent disruption of the respiratory mucosa. Tracheal cytotoxin (TCT) is the only virulence factor produced by B. pertussis that has been able to recapitulate this pathology in animal models. This pathophysiology is well characterized in a hamster tracheal model, but human data are lacking due to scarcity of donor material. We assessed the impact of TCT and lipopolysaccharide (LPS) on the functional integrity of the human airway mucosa by using in vitro airway mucosa models developed by co-culturing human tracheobronchial epithelial cells and human tracheobronchial fibroblasts on porcine small intestinal submucosa scaffold under airlift conditions. TCT and LPS either alone and in combination induced blebbing and necrosis of the ciliated epithelia. TCT and LPS induced loss of ciliated epithelial cells and hyper-mucus production which interfered with mucociliary clearance. In addition, the toxins had a disruptive effect on the tight junction organization, significantly reduced transepithelial electrical resistance and increased FITC-Dextran permeability after toxin incubation. In summary, the results indicate that TCT collaborates with LPS to induce the disruption of the human airway mucosa as reported for the hamster tracheal model.The tick vector Rhipicephalus sanguineus is established as a complex of closely related species with high veterinary-medical significance, in which the presence of different genetic, morphological, and biological traits has resulted in the recognition of different lineages within taxa. One of the most striking differences in the "temperate" and "tropical" lineages of R. AZ 3146 sanguineus (s.l.) is the vector competence to Ehrlichia canis, suggesting that these ticks tolerate and react differently to pathogen infection. The present study addresses the SG and MG proteome of the R. sanguineus tropical and temperate lineages and compares their proteomic profile during E. canis infection. Batches of nymphs from the two lineages were allowed to feed on naïve and experimentally E. canis infected dogs and after molting, adults were dissected, and salivary glands and midgut tissues separated. Samples were screened for the presence of E. canis before proteomic analyses. The representation of the proteins identified in infecte control.The study of the gut microbiota-brain axis has become an intriguing field, attracting attention from both gastroenterologists and neurobiologists. The hippocampus is the center of learning and memory, and plays a pivotal role in neurodegenerative diseases, such as Alzheimer's disease (AD). Previous studies using diet administration, antibiotics, probiotics, prebiotics, germ-free mice, and fecal analysis of normal and specific pathogen-free animals have shown that the structure and function of the hippocampus are affected by the gut microbiota. Furthermore, hippocampal pathologies in AD are positively correlated with changes in specific microbiota. Genomic and neurochemical analyses revealed significant alterations in genes and amino acids in the hippocampus of AD subjects following a remarkable shift in the gut microbiota. In a recent study, when young animals were transplanted with fecal microbiota derived from AD patients, the recipients showed significant impairment of cognitive behaviors, AD pathologies, and changes in neuronal plasticity and cytokines.