Therapeutic Potential of IL-9 in Allergic and Autoimmune Diseases

Interleukin-9 (IL-9) is a pleiotropic cytokine produced by several immune and epithelial cells. Recently, many studies have eluded the physiological and pathological roles of IL-9 and its lineage-specific helper T cell subset (Th9). In this chapter, we will focus on the immunological role of Interleukin 9 (IL-9) in allergy and autoimmunity. We will introduce the basics of IL-9 and describe the cells involved in the secretion, signaling, and regulation of IL-9. After establishing the background, we will discuss the pathogenesis and regulation of IL-9 in allergic and autoimmune diseases. We will conclude the chapter by providing an updated therapeutics that target IL-9 and their potential uses in autoimmune and allergic diseases

An Eye on Staphylococcus aureus Toxins: Roles in Ocular Damage and Inflammation

Staphylococcus aureus (S. aureus) is a common pathogen of the eye, capable of infecting external tissues such as the tear duct, conjunctiva, and the cornea, as well the inner and more delicate anterior and posterior chambers. S. aureus produces numerous toxins and enzymes capable of causing profound damage to tissues and organs, as well as modulating the immune response to these infections. Unfortunately, in the context of ocular infections, this can mean blindness for the patient. The role of α-toxin in corneal infection (keratitis) and infection of the interior of the eye (endophthalmitis) has been well established by comparing virulence in animal models and α-toxin-deficient isogenic mutants with their wild-type parental strains. The importance of other toxins, such as β-toxin, γ-toxin, and Panton–Valentine leukocidin (PVL), have been analyzed to a lesser degree and their roles in eye infections are less clear. Other toxins such as the phenol-soluble modulins have yet to be examined in any animal models for their contributions to virulence in eye infections. This review discusses the state of current knowledge of the roles of S. aureus toxins in eye infections and the controversies existing as a result of the use of different infection models. The strengths and limitations of these ocular infection models are discussed, as well as the need for physiological relevance in the study of staphylococcal toxins in these models

S-layer Impacts the Virulence of Bacillus in Endophthalmitis

International audiencePurpose: Bacillus causes a sight-threating infection of the posterior segment of the eye. The robust intraocular inflammatory response in this disease is likely activated via host innate receptor interactions with components of the Bacillus cell envelope. S-layer proteins (SLPs) of some Gram-positive pathogens contribute to the pathogenesis of certain infections. The potential contributions of SLPs in eye infection pathogenesis have not been considered. Here, we explored the role of a Bacillus SLP (SlpA) in endophthalmitis pathogenesis.Methods: The phenotypes and infectivity of wild-type (WT) and S-layer deficient (ΔslpA) Bacillus thuringiensis were compared. Experimental endophthalmitis was induced in C57BL/6J mice by intravitreally injecting 100-CFU WT or ΔslpA B. thuringiensis. Infected eyes were analyzed by bacterial counts, retinal function analysis, histology, and inflammatory cell influx. SLP-induced inflammation was also analyzed in vitro. Muller cells (MIO-M1) were treated with purified SLP. Nuclear factor-κB (NF-κB) DNA binding was measured by ELISA and expression of proinflammatory mediators from Muller cells was measured by RT-qPCR.Results: Tested phenotypes of WT and ΔslpA B. thuringiensis were similar, with the exception of absence of the S-layer in the ΔslpA mutant. Intraocular growth of WT and ΔslpA B. thuringiensis was also similar. However, eyes infected with the ΔslpA mutant had significantly reduced inflammatory cell influx, less inflammatory damage to the eyes, and significant retention of retinal function compared with WT-infected eyes. SLP was also a potent stimulator of the NF-κB pathway and induced the expression of proinflammatory mediators (IL6, TNFα, CCL2, and CXCL-1) in human retinal Muller cells.Conclusions: Taken together, our results suggest that SlpA contributes to the pathogenesis of Bacillus endophthalmitis, potentially by triggering innate inflammatory pathways in the retina