PTX3 protects from CMV infection and reactivation in vivo. (A-B) BALB/c or C57BL6, PTX3+/+, and PTX3–/– mice were infected intraperitoneally with MCMV. Virus titers, expressed as log10 (mean ± SE), were quantified on MEF cells by standard plaque assay on tissues removed at different times. PTX3 and GCV were administered intraperitoneally beginning on the day of the infection. Controls received the diluent alone. Results are representative of 4 independent experiments. (C) Histologic analysis of periodic acid–Schiff–stained lung sections from PTX3+/+ and PTX3–/– mice infected with MCMV and treated (+) or not (–) with PTX3 for a week. Cellular recruitment associated with signs of parenchimal destruction, peribrochial fibrosis, and Globet cell hyperplasia (magnified × 20 in the insets; a 20×/0.45 objective lens was used) were seen in PTX3–/– more than PTX3+/+ mice and were ameliorated by PTX3 treatment. Histology was done 1 day after treatment. Magnification, × 10 in all panels; obtained with a10×/0.25 objective lens. (D) BALB/c or C57BL6 mice were infected with MCMV as described for panel A. Three months later, MCMV latency was confirmed by the absence of acute MCMV infection in spleen and lung. Infected mice were used either as recipients of allogeneic donor uninfected bone marrow cells (MCMV+ recipients) or as donors of bone marrow cells (MCMV+ donors) to be injected into uninfected recipients. PTX3 (1 mg/kg intraperitoneally) was given daily for 2 weeks, starting the day after HSCT. Dying or surviving mice (killed 30 days after HSCT) were assessed for MCMV viral loads in the lungs by the plaque assay. MST indicates median survival time (days). Bars indicate the standard errors. *P < .05, treated versus untreated mice. (E) MCMV-infected BALB/c mice received Aspergillus conidia intravenously 2 weeks after the viral infection and subsequent treatment with PTX3 (1 mg/kg intraperitoneally) daily for 1 week. Quantification of fungal growth was done 3 days after infection by the chitin assay and results are expressed as chitin content (micrograms of glucosamine/organ). MST indicates median survival time. IL-12p70 levels were assessed in lung homogenates and the frequency of IFN-γ–producing cells was assessed in purified CD4+ T cells from spleens 3 days after Aspergillus-infection by specific ELISA or ELISPOT assays. Bars indicate the standard errors. *P < .05, MCMV-infected versus uninfected mice. **P < .05, PTX3-treated versus untreated MCMV-infected mice.
