Exploring the Role of Innate Lymphocytes in the Immune System of Bats and Virus-Host Interactions

Bats are reservoirs of a large number of viruses of global public health significance, including the ancestral virus for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the causative agent of coronavirus disease 2019 (COVID-19). Although bats are natural carriers of multiple pathogenic viruses, they rarely display signs of disease. Recent insights suggest that bats have a more balanced host defense and tolerance system to viral infections that may be linked to the evolutionary adaptation to powered flight. Therefore, a deeper understanding of bat immune system may provide intervention strategies to prevent zoonotic disease transmission and to identify new therapeutic targets. Similar to other eutherian mammals, bats have both innate and adaptive immune systems that have evolved to detect and respond to invading pathogens. Bridging these two systems are innate lymphocytes, which are highly abundant within circulation and barrier tissues. These cells share the characteristics of both innate and adaptive immune cells and are poised to mount rapid effector responses. They are ideally suited as the first line of defense against early stages of viral infections. Here, we will focus on the current knowledge of innate lymphocytes in bats, their function, and their potential role in host–pathogen interactions. Moreover, given that studies into bat immune systems are often hindered by a lack of bat-specific research tools, we will discuss strategies that may aid future research in bat immunity, including the potential use of organoid models to delineate the interplay between innate lymphocytes, bat viruses, and host tolerance.

Non-Invasive Transcutaneous Vagus Nerve Stimulation for the Treatment of Fibromyalgia Symptoms: A Study Protocol

Stimulation of the vagus nerve, a parasympathetic nerve that controls the neuro-digestive, vascular, and immune systems, induces pain relief, particularly in clinical conditions such as headache and rheumatoid arthritis. Transmission through vagal afferents towards the nucleus of the solitary tract (NST), the central relay nucleus of the vagus nerve, has been proposed as the main physiological mechanism that reduces pain intensity after vagal stimulation. Chronic pain symptoms of fibromyalgia patients might benefit from stimulation of the vagus nerve via normalization of altered autonomic and immune systems causing their respective symptoms. However, multi-session non-invasive vagal stimulation effects on fibromyalgia have not been evaluated in randomized clinical trials. We propose a parallel group, sham-controlled, randomized study to modulate the sympathetic–vagal balance and pain intensity in fibromyalgia patients by application of non-invasive transcutaneous vagus nerve stimulation (tVNS) over the vagal auricular and cervical branches. We will recruit 136 fibromyalgia patients with chronic moderate to high pain intensity. The primary outcome measure will be pain intensity, and secondary measures will be fatigue, health-related quality of life, sleep disorders, and depression. Heart rate variability and pro-inflammatory cytokine levels will be obtained as secondary physiological measures. We hypothesize that multiple tVNS sessions (five per week, for 4 weeks) will reduce pain intensity and improve quality of life as a result of normalization of the vagal control of nociception and immune–autonomic functions. Since both vagal branches project to the NST, we do not predict significantly different results between the two stimulation protocols.

Ivermectin (IVM) Possible Side Activities and Implications in Antimicrobial Resistance and Animal Welfare: The Authors’ Perspective

Ivermectin has a wide number of many diverse functions. Certainly, it is irreplaceable for the treatment of parasitic pathologies in both human and veterinary medicine, and the latter represents the major field of its application. It has been called the “drug for the world’s poor” because of its role as a saviour for those living on the margins of society, in underdeveloped areas afflicted by devastating and debilitating diseases, such as Onchocerciasis and Lymphatic filariasis. It showed huge, unexpected potential as an antibacterial (Chlamydia trachomatis and mycobacteria), and it has antiviral and anti-inflammatory properties. The research line described here is placed right in the middle of the investigation on the impact of this drug as an antimicrobial and an immunomodulator. Being a drug widely employed for mass administration, it is mandatory to broaden the knowledge of its possible interaction with bacterial growth and its generation of antimicrobial resistance. Equally, it is important to understand the impact of these drugs on the immune systems of animal species, e.g., horses and dogs, in which this drug is often used. More importantly, could immunomodulation and antibacterial activity promote both bacterial growth and the occurrence of resistance mechanisms?

Immune dysfunction in chronic kidney disease

Chronic kidney disease is characterized by immune dysfunction that increases predisposition to infections, virus-associated cancers and impaired response to vaccination. The altered immune response is caused by impairment of both innate and adaptive immune systems, as well as other factors that are hallmarks of renal disease, such as uremia, malnutrition, chronic inflammation, mineral bone disease and anemia. The aim of this article is to review the causes and mechanisms that lead to immune dysfunction in patients with chronic kidney disease.

Control of bacterial anti-phage signaling by a WYL domain transcription factor

Bacteria use diverse immune systems to defend themselves from ubiquitous viruses termed bacteriophages (phages). Many anti-phage systems function by abortive infection to kill a phage-infected cell, raising the question of how these systems are regulated to avoid activation and cell killing outside the context of infection. Here, we identify a transcription factor associated with the widespread CBASS bacterial immune system, that we term CapW. CapW forms a homodimer and binds a palindromic DNA sequence in the CBASS promoter region. Two crystal structures of CapW reveal how the protein switches from a DNA binding-competent state to a ligand-bound state that cannot bind DNA due to misalignment of dimer-related DNA binding domains. We show that CapW strongly represses CBASS gene expression in uninfected cells, and that CapW disruption likely results in toxicity due to uncontrolled CBASS expression. Our results parallel recent findings with BrxR, a transcription factor associated with the BREX anti-phage system, and suggest that CapW and BrxR are the founding members of a family of universal anti-phage signaling proteins.

A Review of the Prevalence and Diagnostic Points of Cryptosporidium Species in Immunocompromised and Healthy Human Samples in Iran

Cryptosporidium species are important intestinal pathogens with widespread distribution in humans and other hosts. Whereas the parasite causes acute and self-limiting gastroenteritis in people with healthy immune systems, many reports on this infection around the world are limited to people with defective or suppressed immune systems who suffer from a persistent and deadly infection. Using laboratory-serological and molecular methods for the detection of Cryptosporidium species in immunocompromised and healthy human samples, recent studies in Iran indicated that the prevalence of Cryptosporidium species in different samples varied between 0 to 14%. The samples in Iranian studies included human fecal and diarrheic samples from diarrheic children, patients with gastroenteritis, immunocompromised individuals, and people in contact with livestock. Furthermore, some species were reported based on molecular studies including Cryptosporidium parvum and Cryptosporidium hominis. Some studies have also reported Cryptosporidium meleagridis. In this review study, data were collected regarding the prevalence of cryptosporidiosis in high-risk individuals such as children and immunocompromised individuals. The results revealed that the higher prevalence of C. parvum in Iranian studies in the last 10 years may be attributed to the transmission of infection from animal sources.

Infection, inflammation and thrombosis: a review of potential mechanisms mediating arterial thrombosis associated with influenza and severe acute respiratory syndrome coronavirus 2

Thrombosis has long been reported as a potentially deadly complication of respiratory viral infections and has recently received much attention during the global coronavirus disease 2019 pandemic. Increased risk of myocardial infarction has been reported during active infections with respiratory viruses, including influenza and severe acute respiratory syndrome coronavirus 2, which persists even after the virus has cleared. These clinical observations suggest an ongoing interaction between these respiratory viruses with the host’s coagulation and immune systems that is initiated at the time of infection but may continue long after the virus has been cleared. In this review, we discuss the epidemiology of viral-associated myocardial infarction, highlight recent clinical studies supporting a causal connection, and detail how the virus’ interaction with the host’s coagulation and immune systems can potentially mediate arterial thrombosis.