No abstract

Viruses have been suspected as causes and contributors of human autoimmune diseases (AID), although direct evidence for the association is lacking. However, several animal models provide strong evidence that viruses can induce AIDs as well as act to accelerate and exacerbate lesions in situations where self-tolerance is broken. Many models support the hypothesis by acting as molecular mimics that stimulate self-reactive lymphocytes. Mimicry alone is usually inadequate and with human AID, no compelling evidence supports a role for viruses that are acting as molecular mimics. Alternative mechanisms by which viruses participate in autoimmunity are non-specific, involving a mechanistically poorly understood process termed bystander activation or perhaps viral interference with regulatory cell control systems. This review briefly discusses examples where viruses are involved, taking the view point that molecular mimicry is over emphasized as a critical mechanism during AID pathogenesis.

Herpes simplex virus (HSV) infection of the cornea culminates in an immunopathological lesion (stromal keratitis -SK) that impairs vision. This report shows that HSV infection results in IL-23 up-regulation, but if this response fails to occur, as was noted in p19-/-mice, the severity of lesions, their incidence and the level of viral induced angiogenesis were significantly increased compared to wild-type (WT) animals (p < 0.05). The higher disease severity in p19-/-mice appeared to be the consequence of an increased IL-12 response that in turn led to the induction of higher numbers of IFN-γ producing CD4 + T cells, the principal orchestrators of SK. Our results indicate that the severity of HSV induced immunopathological lesions may be mainly the consequence of IL-12 driven Th1 T cell reactions rather than the action of IL-17 producing cells controlled by IL-23.

Chemokines are important chemoattractant inflammatory molecules, but their interdependent network in disease pathogenesis remains unclear. Studies in mouse models have shown that herpetic stromal keratitis (SK) is produced by the consequence of a tissue-destructive immunoinflammatory reaction involving herpes simplex virus type 1 (HSV) infection. Here we found that ocular HSV infection leads to increased expression of monocyte chemoattractant protein-1 (MCP-1), one of the major chemoattractants for immune cells that express CCR2, in the SK cornea. However, MCP-1 is unlikely to be a chemoattractant for infiltrating Gr-1(+), CD11b(+) cells in SK, as these cells are found to be CCR2 negative. Nevertheless, infection of MCP-1(-/-) mice resulted in more severe SK lesion severity compared with WT mice (P<0.01). We demonstrated that the loss of MCP-1 in the SK cornea caused a significant overexpression of macrophage inflammatory protein-2 (MIP-2) (P<0.01) on days 2 and 4 postinfection and increased infiltration of inflammatory cells (Gr-1-high and CD11b(+)) expressing CXCR2, a receptor for MIP-2, into the cornea. Subsequently, increased infiltration of inflammatory cells accelerated by MIP-2 overexpression might result in the high production of inflammatory molecules, including vascular endothelial growth factor (VEGF) and IL-1beta in SK, as well as CpG oligodeoxynucleotide (ODN)-implanted eyes of MCP-1(-/-) mice. These results indicate that MCP-1 in the SK cornea might regulate the expression of other chemokines, as well as the infiltration of inflammatory cells and control development of SK.

Pseudomonas aeruginosa, a gram negative, multiple drug-resistant (MDR) biofilm forming organism associated with nosocomial infections, is the causative agent of several life-threatening diseases. Emergence of multiple drug resistance against current generation antibiotics in such pathogens is a serious problem for medical practitioners. An alternative means to control the MDR pathogens is combination therapy of antibiotic with suitable biological control measures such as lytic bacteriophages. In this study, we report the isolation and characterization of P. aeruginosa specific phage vB_PaeM_P6 which is used in combination with subminimal inhibitory concentrations (MIC) of ciprofloxacin for the control of P. aeruginosa biofilm. Synergistic activity of phage 0.05 multiplicity of infection and sub-MIC ciprofloxacin (0.75 µg/ml) treatment is reported for the inhibition of biofilm forming as well as preformed biofilms of five clinical strains of P. aeruginosa.