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

Histopathological characteristics of a novel knock-in mouse prostate cancer model

Prostate cancer is relatively unique to man. There is no naturally occurring prostate cancer in the mouse. Pre-clinical studies involve the establishment of a genetically engineered mouse prostate cancer model with features close to those of the human situation. A new knock-in mouse adenocarcinoma prostate (KIMAP) model was established, which showed close-to-human kinetics of tumor development. In order to determine if the similar kinetics is associated with heterogeneous tumor architecture similar to the human situation, we utilized a new mouse histological grading system (Gleason analogous grading system) similar to the Gleason human grading system and flow cytometry DNA analysis to measure and compare the adenocarcinoma of the KIMAP model with human prostate cancer. Sixty KIMAP prostate cancer samples from 60 mice were measured and compared with human prostate cancer. Flow cytometry DNA analysis was performed on malignant prostate tissues obtained from KIMAP models. Mice with prostate cancer from KIMAP models showed a 53.3% compound histological score rate, which was close to the human clinical average (50%) and showed a significant correlation with age (P = 0.001). Flow cytometry analyses demonstrated that most KIMAP tumor tissues were diploid, analogous to the human situation. The similarities of the KIMAP mouse model with tumors of the human prostate suggest the use of this experimental model to complement studies of human prostate cancer

Ethnic Differences in Body Mass Index Trajectories from Adolescence to Adulthood: A Focus on Hispanic and Asian Subgroups in the United States

BACKGROUND: Compared to whites, U.S. Hispanics have higher obesity rates; U.S. Asians have lower rates. However Hispanics and Asians are each comprised of several ethnic subgroups that differ with respect to country of origin, immigration history, and geographic distribution across the U.S. Among adolescents, ethnic differences in obesity have been previously reported, but no studies have examined longitudinal change in body mass index (BMI) by Hispanic and Asian subgroup category to understand when and why these disparities emerge, especially during the critical transition between adolescence and adulthood. METHODS: Using nationally-representative, longitudinal data from 1355 Hispanics (Mexican, Puerto Rican, Cuban, Central/South American, Other Hispanic), 520 Asians (Chinese, Filipino, Other Asian), and 5061whites from the National Longitudinal Study of Adolescent Health (Waves II–IV: 1996–2009), we used linear mixed spline models to examine whether Hispanic and Asian adolescent subgroups shared the same BMI trajectories as whites as they aged into adulthood. We also investigated the role of social and behavioral factors in explaining race/ethnic differences. RESULTS: Among Hispanics, Mexican and Puerto Rican-origin individuals exhibited faster increases in BMI both in adolescence and in adulthood and these patterns were not attributable to the measured social and behavioral factors. There was also evidence of emerging disparities in Cuban males, and in Central/South Americans relative to whites. In contrast, Chinese, Filipino, and Other Asian adolescents had significantly lower BMI and slower BMI increases in adulthood compared to whites. In models adjusted for social and behavioral factors, Chinese-white and Other Asian-white differentials remained unexplained. CONCLUSIONS: Aggregate estimates of Hispanics and Asians mask important heterogeneity in BMI. A better understanding of weight dynamics early in the life course can inform how and when disparities emerge to better target prevention efforts