We explore the controversial issue of the role of eosinophils in host defense against helminthic parasites using the established Schistosoma mansoni infection model in 2 novel mouse models of eosinophil lineage ablation (⌬dblGATA and TgPHIL). No eosinophils were detected in bone marrow of infected ⌬dblGATA or TgPHIL mice, despite the fact that serum IL-5 levels in these infected mice exceeded those in infected wild type by approximately 4-fold. Liver granulomata from infected ⌬dblGATA and TgPHIL mice were likewise depleted of eosinophils compared with those from their respective wild types. No eosinophil-dependent differences in granuloma number, size, or fibrosis were detected at weeks 8 or 12 of infection, and differential accumulation of mast cells was observed among the ⌬dblGATA mice only at week 12. Likewise, serum levels of liver transaminases, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) increased in all mice in response to S mansoni infection, with no eosinophil-dependent differences in hepatocellular damage observed. Finally, eosinophil ablation had no effect on worm burden or on egg deposition. Overall, our data indicate that eosinophil ablation has no impact on traditional measures of disease in the S mansoni infection model in mice. IntroductionThe role of eosinophils in host defense and disease remains controversial, and the debate continues as to whether these cells are active participants or simply bystanders in various pathophysiologic states. This is particularly so with respect to disease caused by helminthic parasites. While it would seem logical to assume that eosinophils should provide a measure of host defense against these important and endemic infections, as they are elicited in large numbers in response to helminth infection, and they degranulate on and cause damage to various forms of the parasitic helminthes in various in vitro settings, the results from numerous experiments performed in vivo have been equivocal. [1][2][3] The cytokine-mediated pathogenesis of the well-characterized mouse model of helminth infection, Schistosoma mansoni, has been described in great detail. [4][5][6][7] This infection includes a prominent Th2 phase, resulting in an increase in serum interleukin-5 (IL-5) in response to egg deposition in the portal circulation at weeks 6 to 8 after exposure to water-borne cercariae. Increased serum IL-5 results in massive bone marrow and blood eosinophilia. Eosinophils are recruited specifically to the developing liver granulomata, the site of active inflammation and tissue remodeling. Several eosinophil components implicated in debris scavenging and tissue remodeling activity include the eosinophil peroxidase, 8 the ribonucleases, 9 matrix metalloproteinases, 10 and the protease inhibitor, plasminogen activator inhibitor-2 (PAI-2). 11 Eosinophils may also play an important role in maintaining the Th2 response to infection via secretion of endogenous 13 Several groups began the exploration of the role of eosinophils in host defense against helmint...

Herpes simplex viruses (HSV) reactivate at rates proportional to the viral loads in latently infected ganglia. However, these rates vary substantially among infected animals. We assessed whether the numbers of HSVspecific CD8؉ T cells infiltrating latently infected ganglia also affect reactivation rates and contribute to their variability. Following corneal infection of mice with HSV type 2 (HSV-2), we quantified the latent viral loads in dissociated trigeminal ganglia by real-time PCR, the numbers of infiltrating CD8 ؉ T cells by flow cytometry, and the rates of reactivation by the detection of cell-free virus released from ganglion cells cultured in 96-well plates. The reactivation rates correlated directly with the latent viral loads (P ‫؍‬ 0.001) but did so more strongly (P ‫؍‬ 10 ؊7 ) when cultures were depleted of CD8 ؉ T cells. Reactivation rates were reduced in a dose-dependent fashion by adding back ganglion CD8؉ T cells to the cultures (P ‫؍‬ 0.003). We related the latent viral loads, numbers of CD8 ؉ T cells, and reactivation rates by mathematical equations. The rates of reactivation predicted from latent viral loads and numbers of infiltrating CD8 ؉ T cells in dissociated ganglia correlated with the observed rates of reactivation (P ‫؍‬ 0.04). The reactivation of HSV-2 from ganglia ex vivo is determined both by the latent viral load and the number of infiltrating CD8 ؉ T cells.The establishment of neuronal latency and periodic reactivation are definitive features of herpes simplex virus (HSV) infections in animals and humans. While the determinants of reactivation rates in humans are not well defined, the competence of the host cellular immune response is thought to be important in controlling reactivation (22,43). In animals, the quantity of latent HSV type 1 (HSV-1) DNA in ganglia (the latent viral load) as estimated by levels of latency-associated transcripts (13, 16) and more precisely by quantitative PCR of viral DNA (29,(33)(34)(35) is an important determinant of recurrence rates ex vivo. We confirmed this association in vivo, as well, using infected guinea pigs in which genital disease due to HSV-1 or HSV-2 recurs spontaneously (17,25).Within individual studies, recurrence rates of HSV infection vary up to 10-fold, even among animals with comparable latent viral loads (17). Presumably, in these animals, other factors in addition to latent viral loads contribute to reactivation rates. An important clue to the nature of such factors was provided in recent seminal reports by Khanna et al. and Liu et al., who showed that HSV-specific, gamma interferon (IFN-␥)-positive, CD8 ϩ T cells infiltrate latently infected mouse trigeminal ganglia (TG) and block the reactivation of HSV-1 from latency ex vivo in a dose-dependent manner (19,20,27). Neither HSV-1 nor HSV-2 undergoes spontaneous reactivation as defined by the production of infectious virus in mice; however, more sensitive molecular techniques have demonstrated low levels of spontaneous viral antigens and productive cycle transcripts in ganglia ...