Molecular mechanisms of autoimmunity triggered by microbial infection

Autoimmunity can be triggered by microbial infection. In this context, the discovery of Toll-like receptors (TLRs) provides new insights and research perspectives. TLRs induce innate and adaptive antimicrobial immune responses upon exposure to common pathogen-associated molecules, including lipopeptides, lipopolysaccharides, and nucleic acids. They also have the potential, however, to trigger autoimmune disease, as has been revealed by an increasing number of experimental reports. This review summarizes important facts about TLR biology, available data on their role in autoimmunity, and potential consequences for the management of patients with autoimmune disease

Toll-like receptor-4: Renal cells and bone marrow cells signal for neutrophil recruitment during pyelonephritis

Toll-like receptor-4: Renal cells and bone marrow cells signal for neutrophil recruitment during pyelonephritis.BackgroundThe molecular mechanisms of pathogen recognition that initiate infective pyelonephritis are poorly understood. Toll-like receptor-4 (TLR4) mutant mice infected with uropathogenicEscherichia coli lack renal CXCL2 mRNA expression, subsequent neutrophil recruitment, and renal abscess formation.MethodsWe used a bone marrow transplant approach in order to investigate the contribution of TLR4 in intrinsic renal cells or bone-marrow-derived immune cells to neutrophil recruitment during infective pyelonephritis.ResultsBoth chimera either expressing mutanttlr4 in intrinsic renal cells and wild-typetlr4 in bone marrow-derived cells or vice versa showed an impaired response to uropathogenicE. coli infection in terms of leukocyturia and renal abscess formation when compared totlr4 wild-type mice with congenic bone marrow transplants.ConclusionThese data suggest that TLR4 is required on both intrinsic renal cells (e.g., tubular epithelial cells) and bone marrow-derived immune cells for the control of ascending uropathogenicE. coli infection by initiating chemokine-driven renal neutrophil recruitment