SUMMARY A distinctive feature of the cytomegaloviruses is their wide tissue tropism, demonstrated by the infection of many organs and cell types in an active infection. However, in experimental models of systemic infection, the earliest stages of infection are not well characterized, and it is unclear whether only certain cells are initially infected. Using a recombinant murine cytomegalovirus (MCMV) expressing green fluorescent protein (GFP), we tracked viral infection after systemic administration via intraperitoneal injection and showed that specific cells are infected within the first hours. We provide evidence that MCMV trafficked as free virus from the peritoneal cavity into the mediastinal lymphatics, providing access to the bloodstream. We demonstrate that it productively infected CD169+ subcapsular sinus macrophages in the mediastinal lymph nodes, ER-TR7+ CD29+ reticular fibroblasts in the spleen, and hepatocytes. Infection in the spleen followed a distinctive pattern, beginning in the marginal zone at 6h and spreading into red pulp by 17h. By 48h after infection, there was widespread infection in the spleen and liver with degeneration of infected cells. In addition, infected dendritic cells appeared in the white pulp of the spleen at 48h post infection. On the other hand, cowpox virus showed a different pattern of infectivity in the spleen and liver. Thus, early MCMV infection produces a distinct pattern with infection of selective cells.

The selectin family of adhesion molecules mediates the recruitment of immune cells to the site of inflammation, which is critical for host survival of infection. To characterize the role of selectins in host defense against Salmonella Typhimurium infection, wild-type (WT) mice and mice lacking P-selectin glycoprotein ligand-1 (PSGL-1), P-, E-, or L-selectin, or the glycosyltransferase C2GlcNAcT-I (core 2) were infected using a Salmonella acute gastroenteritis model. Mice were monitored for survival and assessed for intestinal inflammation at 1 and 4 days postinfection. Infected mice lacking core 2, PSGL-1, or P-selectin showed a more pronounced morbidity and a significantly higher mortality rate associated with higher bacterial load and proinflammatory cytokine production, including that of TNF-α, MCP-1, and IL-6, from the colons at 4 days postinfection as compared with WT control. Surprisingly, at 1 day postinfection, more severe inflammation and higher neutrophil infiltration were observed in the ceca of mice lacking core 2, PSGL-1, or P-selectin compared with WT control. Enhanced levels of α4β7+ and MAdCAM-1+ cells were observed in the ceca of infected mice lacking core 2, PSGL-1, or P-selectin. Neutrophil recruitment, cecal inflammation, and mortality rates were dramatically reduced in infected P-selectin knockout mice receiving blocking mAb to α4β7 integrin, indicating that this alternative adhesion molecule may attempt to compensate for the loss of selectins in neutrophil recruitment. These results demonstrate a definitive phenotypic abnormality in mice lacking core 2, PSGL-1, or P-selectin, suggesting that the interaction of functional PSGL-1 with P-selectin is an important process in host defense against Salmonella infection.

An 8 yr old male English bulldog receiving treatment for immune-mediated thrombocytopenia was diagnosed with calcinosis cutis 90 days after initiation of corticosteroid therapy. Twenty-four days later, the patient presented in a comatose state after collapsing and was euthanized. Postmortem examination revealed coronary arteriosclerosis and myocardial infarction leading to congestive heart failure. Calcinosis cutis and myocardial necrosis were most likely complications associated with administration of corticosteroids in this dog. Important implications regarding the classification of calcinosis cutis and the use of immunosuppressive doses of corticosteroids are discussed.

Graft failure accounted for approximately 30% to 40% of indications for keratoplasties at three academic centers from 2002 to 2012, which was more than double and in some cases triple that of the EBAA data during this period. These higher frequencies of regrafting may represent a referral bias of patients with complicated cases to academic centers who then require multiple keratoplasties.