Brucella abortus Uses a Stealthy Strategy to Avoid Activation of the Innate Immune System during the Onset of Infection

To unravel the strategy by which Brucella abortus establishes chronic infections, we explored its early interaction with innate immunity. Methodology/Principal Findings Brucella did not induce proinflammatory responses as demonstrated by the absence of leukocyte recruitment, humoral or cellular blood changes in mice. Brucella hampered neutrophil (PMN) function and PMN depletion did not influence the course of infection. Brucella barely induced proinflammatory cytokines and consumed complement, and was strongly resistant to bactericidal peptides, PMN extracts and serum. Brucella LPS (BrLPS), NH-polysaccharides, cyclic glucans, outer membrane fragments or disrupted bacterial cells displayed low biological activity in mice and cells. The lack of proinflammatory responses was not due to conspicuous inhibitory mechanisms mediated by the invading Brucella or its products. When activated 24 h post-infection macrophages did not kill Brucella, indicating that the replication niche was not fusiogenic with lysosomes. Brucella intracellular replication did not interrupt the cell cycle or caused cytotoxicity in WT, TLR4 and TLR2 knockout cells. TNF-α-induction was TLR4- and TLR2-dependent for live but not for killed B. abortus. However, intracellular replication in TLR4, TLR2 and TLR4/2 knockout cells was not altered and the infection course and anti-Brucella immunity development upon BrLPS injection was unaffected in TLR4 mutant mice. Conclusion/Significance We propose that Brucella has developed a stealth strategy through PAMPs reduction, modification and hiding, ensuring by this manner low stimulatory activity and toxicity for cells. This strategy allows Brucella to reach its replication niche before activation of antimicrobial mechanisms by adaptive immunity. This model is consistent with clinical profiles observed in humans and natural hosts at the onset of infection and could be valid for those intracellular pathogens phylogenetically related to Brucella that also cause long lasting infections

An integrated socio-environmental framework for glacier hazard management and climate change adaptation: lessons from Lake 513, Cordillera Blanca, Peru

Glacier hazards threaten societies in mountain regions worldwide. Glacial lake outburst floods (GLOFs) pose risks to exposed and vulnerable populations and can be linked in part to long-term post-Little Ice Age climate change because precariously dammed glacial lakes sometimes formed as glaciers generally retreated after the mid-1800s. This paper provides an interdisciplinary and historical analysis of 40 years of glacier hazard management on Mount Hualcán, at glacial Lake 513, and in the city of Carhuaz in Peru’s Cordillera Blanca mountain range. The case study examines attempted hazard zoning, glacial lake evolution and monitoring, and emergency engineering projects to drain Lake 513. It also analyzes the 11 April 2010 Hualcán rock-ice avalanche that triggered a Lake 513 GLOF; we offer both a scientific assessment of the possible role of temperature on slope stability and a GIS spatial analysis of human impacts. Qualitative historical analysis of glacier hazard management since 1970 allows us to identify and explain why certain actions and policies to reduce risk were implemented or omitted. We extrapolate these case-specific variables to generate a broader socio-environmental framework identifying factors that can facilitate or impede disaster risk reduction and climate change adaptation. Facilitating factors are technical capacity, disaster events with visible hazards, institutional support, committed individuals, and international involvement. Impediments include divergent risk perceptions, imposed government policies, institutional instability, knowledge disparities, and invisible hazards. This framework emerges from an empirical analysis of a coupled social-ecological system and offers a holistic approach for integrating disaster risk reduction and climate change adaptation