Kupffer Cells Hasten Resolution of Liver Immunopathology in Mouse Models of Viral Hepatitis

Kupffer cells (KCs) are widely considered important contributors to liver injury during viral hepatitis due to their pro-inflammatory activity. Herein we utilized hepatitis B virus (HBV)-replication competent transgenic mice and wild-type mice infected with a hepatotropic adenovirus to demonstrate that KCs do not directly induce hepatocellular injury nor do they affect the pathogenic potential of virus-specific CD8 T cells. Instead, KCs limit the severity of liver immunopathology. Mechanistically, our results are most compatible with the hypothesis that KCs contain liver immunopathology by removing apoptotic hepatocytes in a manner largely dependent on scavenger receptors. Apoptotic hepatocytes not readily removed by KCs become secondarily necrotic and release high-mobility group box 1 (HMGB-1) protein, promoting organ infiltration by inflammatory cells, particularly neutrophils. Overall, these results indicate that KCs resolve rather than worsen liver immunopathology

The Ground-Dwelling Arthropod Community of Península Valdés in Patagonia, Argentina

This is the first study based on a planned and intensive sampling effort that describes the community composition and structure of the ground-dwelling arthropod assemblage of Península Valdés (Patagonia). It was carried out using pitfall traps, opened for two weeks during the summers of 2005, 2006 and 2007. A total of 28, 111 individuals were caught. Ants (Hymenoptera: Formicidae) dominated this community, followed by beetles (Coleoptera) and spiders (Araneae). The most abundant species were Pheidole bergi Mayr (Hymenoptera: Formicidae) and Blapstinus punctulatus Solier (Coleoptera: Tenebrionidae). Two new species were very recently described as new based on specimens collected during this study: Valdesiana curiosa Carpintero, Dellapé & Cheli (Hemiptera, Miridae) and Anomaloptera patagonica Dellapé & Cheli (Hemiptera, Oxycarenidae). The order Coleoptera was the most diverse taxa. The distribution of abundance data was best described by the logarithmic series model both at the family and species levels, suggesting that ecological relationships in this community could be controlled by a few factors. The community was dominated by predators from a trophic perspective. This suggests that predation acts as an important factor driving the distribution and abundances of surface-dwelling arthropods in this habitat and as such serves as a key element in understanding desert, above-ground community structure. These findings may also be useful for management and conservation purposes in arid Patagonia

The Ground-Dwelling Arthropod Community of Península Valdés in Patagonia, Argentina

This is the first study based on a planned and intensive sampling effort that describes the community composition and structure of the ground-dwelling arthropod assemblage of Península Valdés (Patagonia). It was carried out using pitfall traps, opened for two weeks during the summers of 2005, 2006 and 2007. A total of 28, 111 individuals were caught. Ants (Hymenoptera: Formicidae) dominated this community, followed by beetles (Coleoptera) and spiders (Araneae). The most abundant species were Pheidole bergi Mayr (Hymenoptera: Formicidae) and Blapstinus punctulatus Solier (Coleoptera: Tenebrionidae). Two new species were very recently described as new based on specimens collected during this study: Valdesiana curiosa Carpintero, Dellapé & Cheli (Hemiptera, Miridae) and Anomaloptera patagonica Dellapé & Cheli (Hemiptera, Oxycarenidae). The order Coleoptera was the most diverse taxa. The distribution of abundance data was best described by the logarithmic series model both at the family and species levels, suggesting that ecological relationships in this community could be controlled by a few factors. The community was dominated by predators from a trophic perspective. This suggests that predation acts as an important factor driving the distribution and abundances of surface-dwelling arthropods in this habitat and as such serves as a key element in understanding desert, above-ground community structure. These findings may also be useful for management and conservation purposes in arid Patagonia

Persistent Hepatitis B Viral Replication in a FVB/N Mouse Model: Impact of Host and Viral Factors

The mechanism underlying the chronicity of hepatitis B virus (HBV) infection has long been an interesting question. However, this mechanism remains unclear largely due to the lack of an animal model that can support persistent HBV replication and allow for the investigation of the relevant immune responses. In this study, we used hydrodynamic injection to introduce HBV replicon DNA into the livers of three different mouse strains: BALB/c, C57BL/6, and FVB/N. Interestingly, we found that an HBV clone persistently replicated in the livers of FVB/N mice for up to 50 weeks but was rapidly cleared from the livers of BALB/c and C57BL/6 mice. Flow cytometric analysis and quantitative reverse transcription PCR analysis of the mouse livers indicated that after DNA injection, FVB/N mice had few intrahepatic activated cytotoxic T lymphocytes (CTLs) and produced low levels of alanine aminotransferase, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and the CXCL9 and CXCL10 chemokines. These findings were in sharp contrast with those observed in BALB/c and C57BL/6 mice, reflecting a strong correlation between the degree of liver inflammation and viral clearance. Mutational analysis further demonstrated that a change of Asn-214 to Ser-214 in the HBV surface antigen rendered the persistent HBV clone clearable in FVB/N mice, which was accompanied by increased levels of activated CTL and upregulated expression of IFN-γ, CXCL9, and CXCL10 in the livers. These results indicate that the heterogeneity of the host factors and viral sequences may influence the immune responses against HBV. An inadequate activation of immune or inflammatory responses can lead to persistent HBV replication in vivo

Nodular inflammatory foci are sites of T cell priming and control of murine cytomegalovirus infection in the neonatal lung.

Neonates, including mice and humans, are highly susceptible to cytomegalovirus (CMV) infection. However, many aspects of neonatal CMV infections such as viral cell tropism, spatio-temporal distribution of the pathogen as well as genesis of antiviral immunity are unknown. With the use of reporter mutants of the murine cytomegalovirus (MCMV) we identified the lung as a primary target of mucosal infection in neonatal mice. Comparative analysis of neonatal and adult mice revealed a delayed control of virus replication in the neonatal lung mucosa explaining the pronounced systemic infection and disease in neonates. This phenomenon was supplemented by a delayed expansion of CD8(+) T cell clones recognizing the viral protein M45 in neonates. We detected viral infection at the single-cell level and observed myeloid cells forming "nodular inflammatory foci" (NIF) in the neonatal lung. Co-localization of infected cells within NIFs was associated with their disruption and clearance of the infection. By 2-photon microscopy, we characterized how neonatal antigen-presenting cells (APC) interacted with T cells and induced mature adaptive immune responses within such NIFs. We thus define NIFs of the neonatal lung as niches for prolonged MCMV replication and T cell priming but also as sites of infection control