Early mucosal sensing of SIV infection by paneth cells induces IL-1ß production and initiates gut epithelial disruption.

HIV causes rapid CD4+ T cell depletion in the gut mucosa, resulting in immune deficiency and defects in the intestinal epithelial barrier. Breakdown in gut barrier integrity is linked to chronic inflammation and disease progression. However, the early effects of HIV on the gut epithelium, prior to the CD4+ T cell depletion, are not known. Further, the impact of early viral infection on mucosal responses to pathogenic and commensal microbes has not been investigated. We utilized the SIV model of AIDS to assess the earliest host-virus interactions and mechanisms of inflammation and dysfunction in the gut, prior to CD4+ T cell depletion. An intestinal loop model was used to interrogate the effects of SIV infection on gut mucosal immune sensing and response to pathogens and commensal bacteria in vivo. At 2.5 days post-SIV infection, low viral loads were detected in peripheral blood and gut mucosa without CD4+ T cell loss. However, immunohistological analysis revealed the disruption of the gut epithelium manifested by decreased expression and mislocalization of tight junction proteins. Correlating with epithelial disruption was a significant induction of IL-1ß expression by Paneth cells, which were in close proximity to SIV-infected cells in the intestinal crypts. The IL-1ß response preceded the induction of the antiviral interferon response. Despite the disruption of the gut epithelium, no aberrant responses to pathogenic or commensal bacteria were observed. In fact, inoculation of commensal Lactobacillus plantarum in intestinal loops led to rapid anti-inflammatory response and epithelial tight junction repair in SIV infected macaques. Thus, intestinal Paneth cells are the earliest responders to viral infection and induce gut inflammation through IL-1ß signaling. Reversal of the IL-1ß induced gut epithelial damage by Lactobacillus plantarum suggests synergistic host-commensal interactions during early viral infection and identify these mechanisms as potential targets for therapeutic intervention.

Spontaneous regression of herniated lumbar discs.

The spontaneous regression of a lumbar herniated disc is a common occurrence. Studies using imaging techniques as well as immunohistologic analyses have attempted to explain the mechanism for regression. However, the exact mechanism remains elusive. Understanding the process by which herniated discs disappear in the absence of surgery may better guide treatment. Recent case reports, radiographic and immunohistologic studies show that the extent of extrusion of the nucleus pulposus is related to a higher likelihood of regression. To our knowledge, Patient 3 is the first report of spontaneous regression occurring within 2 months. This occurrence was discovered intraoperatively. We present three illustrative patients. Patient 1, a 53-year-old man, presented with a large L2-L3 disc herniation. His 2 year follow-up MRI revealed a complete regression of the extruded fragment. Patient 2, a 58-year-old man, presented with an L3-L4 disc herniation with cephalad migration of a free fragment. MRI 9 months later showed no free fragment but progression of a disc bulge. Intraoperative exploration during the L3-L4 microdiscectomy confirmed the absence of the free fragment. Patient 3, a 58-year-old woman, presented with a large L2-L3 disc extrusion with cephalad migration. An imaging study performed 2 months after the initial study revealed an absence of the free fragment. Our case reports demonstrate the temporal variance in disc regression. While the time course and extent of regression vary widely, the rapid time in which regression can occur should caution surgeons contemplating discectomy based on an MRI performed a significant period prior to surgery.