Leukocyte Immunoglobulin-Like Receptors in Regulating the Immune Response in Infectious Diseases: A Window of Opportunity to Pathogen Persistence and a Sound Target in Therapeutics

Immunoregulatory receptors are essential for orchestrating an immune response as well as appropriate inflammation in infectious and non-communicable diseases. Among them, leukocyte immunoglobulin-like receptors (LILRs) consist of activating and inhibitory receptors that play an important role in regulating immune responses modulating the course of disease progression. On the one hand, inhibitory LILRs constitute a safe-guard system that mitigates the inflammatory response, allowing a prompt return to immune homeostasis. On the other hand, because of their unique capacity to attenuate immune responses, pathogens use inhibitory LILRs to evade immune recognition, thus facilitating their persistence within the host. Conversely, the engagement of activating LILRs triggers immune responses and the production of inflammatory mediators to fight microbes. However, their heightened activation could lead to an exacerbated immune response and persistent inflammation with major consequences on disease outcome and autoimmune disorders. Here, we review the genetic organisation, structure and ligands of LILRs as well as their role in regulating the immune response and inflammation. We also discuss the LILR-based strategies that pathogens use to evade immune responses. A better understanding of the contribution of LILRs to host–pathogen interactions is essential to define appropriate treatments to counteract the severity and/or persistence of pathogens in acute and chronic infectious diseases lacking efficient treatments.

The planctomycete Stieleria maiorica Mal15T employs stieleriacines to alter the species composition in marine biofilms

Bacterial strains of the phylum Planctomycetes occur ubiquitously, but are often found on surfaces of aquatic phototrophs, e.g. alga. Despite slower growth, planctomycetes are not outcompeted by faster-growing bacteria in biofilms on such surfaces; however, strategies allowing them to compensate for slower growth have not yet been investigated. Here, we identified stieleriacines, a class of N-acylated tyrosines produced by the novel planctomycete Stieleria maiorica Mal15T, and analysed their effects on growth of the producing strain and bacterial species likely co-occurring with strain Mal15T. Stieleriacines reduced the lag phase of Mal15T and either stimulated or inhibited biofilm formation of two bacterial competitors, indicating that Mal15T employs stieleriacines to specifically alter microbial biofilm composition. The genetic organisation of the putative stieleriacine biosynthetic cluster in strain Mal15T points towards a functional link of stieleriacine biosynthesis to exopolysaccharide-associated protein sorting and biofilm formation.

Cortical remodelling in childhood is associated with genes enriched for neurodevelopmental disorders

Cortical development during childhood and adolescence has been characterised in recent years using metrics derived from Magnetic Resonance Imaging (MRI). Changes in cortical thickness are greatest in the first two decades of life and recapitulate the genetic organisation of the cortex, highlighting the potential early impact of gene expression on differences in cortical architecture over the lifespan. It is important to further our understanding of the possible neurobiological mechanisms that underlie these changes as differences in cortical thickness may act as a potential phenotypic marker of several common neurodevelopmental and psychiatric disorders.In this study, we combine MRI acquired from a large typically-developing childhood population (n=768) with comprehensive human gene expression databases to test the hypothesis that disrupted mechanisms common to neurodevelopmental disorders are encoded by genes expressed early in development and nested within those associated with typical cortical remodelling in childhood.We find that differential rates of thinning across the developing cortex are associated with spatially-varying gradients of gene expression. Genes that are expressed highly in regions of accelerated thinning are expressed predominantly in cortical neurons, involved in synaptic remodeling, and associated with common cognitive and neurodevelopmental disorders. Further, we identify subsets of genes that are highly expressed in the prenatal period and jointly associated with both developmental cortical morphology and neurodevelopmental disorders.

Identification of protein secretion systems in bacterial genomes

Bacteria with two cell membranes (diderms) have evolved complex systems for protein secretion. These systems were extensively studied in some model bacteria, but the characterisation of their diversity has lagged behind due to lack of standard annotation tools. We built models for accurate identification of protein secretion systems and related appendages in bacteria with LPS-containing outer membranes. They can be used with MacSyFinder (standalone program) or online (http://mobyle.pasteur.fr/cgi-bin/portal.py#forms::txsscan). They include protein profiles and information on the system's composition and genetic organisation. They can be used to search for T1SS-T6SS, T9SS, and accessorily for flagella, Type IV and Tad pili. We identified ~10,000 systems in bacterial genomes, where T1SS and T5SS were by far the most abundant and widespread. The recently described T6SSiii and T9SS were restricted to Bacteroidetes, and T6SSii to Francisella. T2SS, T3SS, and T4SS were frequently encoded in single-copy in one locus, whereas most T1SS were encoded in two loci. The secretion systems of diderm Firmicutes were similar to those found in other diderms. Novel systems may remain to be discovered, since some clades of environmental bacteria lacked all known protein secretion systems. Our models can be fully customized, which should facilitate the identification of novel systems.