Efferocytosis is an innate antibacterial mechanism

Mycobacterium tuberculosis persists within macrophages in an arrested phagosome and depends upon necrosis to elude immunity and disseminate. Although apoptosis of M. tuberculosis-infected macrophages is associated with reduced bacterial growth, the bacteria are relatively resistant to other forms of death, leaving the mechanism underlying this observation unresolved. We find that after apoptosis, M. tuberculosis-infected macrophages are rapidly taken up by uninfected macrophages through efferocytosis, a dedicated apoptotic cell engulfment process. Efferocytosis of M. tuberculosis sequestered within an apoptotic macrophage further compartmentalizes the bacterium and delivers it along with the apoptotic cell debris to the lysosomal compartment. M. tuberculosis is killed only after efferocytosis, indicating that apoptosis itself is not intrinsically bactericidal but requires subsequent phagocytic uptake and lysosomal fusion of the apoptotic body harboring the bacterium. While efferocytosis is recognized as a constitutive housekeeping function of macrophages, these data indicate that it can also function as an antimicrobial effector mechanism.Behar, Fortune, and Remold labs for reagents, helpful discussion, and insights. TIM4-blocking antibodies were a generous gift of Vijay Kuchroo. Members of the Harvard Electron Microscopy Core Facility helped in the preparation, staining, and operation of the electron microscope. The Small Animal Biocontainment (ABC) Suite is supported by CFAR 5P30AI060354. T.R.R and S.M.F were supported by CFAR 5P30AI060354, DP2-0d001378, and T32-AI07387. C.N.A. is the recipient of a fellowship from FCT. S.M.B and H.G.R. were supported by R56AI084161 and R01AI072143

Trypanosome Lytic Factor, an Antimicrobial High-Density Lipoprotein, Ameliorates Leishmania Infection

Innate immunity is the first line of defense against invading microorganisms. Trypanosome Lytic Factor (TLF) is a minor sub-fraction of human high-density lipoprotein that provides innate immunity by completely protecting humans from infection by most species of African trypanosomes, which belong to the Kinetoplastida order. Herein, we demonstrate the broader protective effects of human TLF, which inhibits intracellular infection by Leishmania, a kinetoplastid that replicates in phagolysosomes of macrophages. We show that TLF accumulates within the parasitophorous vacuole of macrophages in vitro and reduces the number of Leishmania metacyclic promastigotes, but not amastigotes. We do not detect any activation of the macrophages by TLF in the presence or absence of Leishmania, and therefore propose that TLF directly damages the parasite in the acidic parasitophorous vacuole. To investigate the physiological relevance of this observation, we have reconstituted lytic activity in vivo by generating mice that express the two main protein components of TLFs: human apolipoprotein L-I and haptoglobin-related protein. Both proteins are expressed in mice at levels equivalent to those found in humans and circulate within high-density lipoproteins. We find that TLF mice can ameliorate an infection with Leishmania by significantly reducing the pathogen burden. In contrast, TLF mice were not protected against infection by the kinetoplastid Trypanosoma cruzi, which infects many cell types and transiently passes through a phagolysosome. We conclude that TLF not only determines species specificity for African trypanosomes, but can also ameliorate an infection with Leishmania, while having no effect on T. cruzi. We propose that TLFs are a component of the innate immune system that can limit infections by their ability to selectively damage pathogens in phagolysosomes within the reticuloendothelial system

Human and murine clonal CD8+ T cell expansions arise during tuberculosis because of TCR selection

The immune system can recognize virtually any antigen, yet T cell responses against several pathogens, including Mycobacterium tuberculosis, are restricted to a limited number of immunodominant epitopes. The host factors that affect immunodominance are incompletely understood. Whether immunodominant epitopes elicit protective CD8+ T cell responses or instead act as decoys to subvert immunity and allow pathogens to establish chronic infection is unknown. Here we show that anatomically distinct human granulomas contain clonally expanded CD8+ T cells with overlapping T cell receptor (TCR) repertoires. Similarly, the murine CD8+ T cell response against M. tuberculosis is dominated by TB10.44-11-specific T cells with extreme TCRß bias. Using a retro genic model of TB10.44-11-specific CD8+ Tcells, we show that TCR dominance can arise because of competition between clonotypes driven by differences in affinity. Finally, we demonstrate that TB10.4-specific CD8+ T cells mediate protection against tuberculosis, which requires interferon-? production and TAP1-dependent antigen presentation in vivo. Our study of how immunodominance, biased TCR repertoires, and protection are inter-related, provides a new way to measure the quality of T cell immunity, which if applied to vaccine evaluation, could enhance our understanding of how to elicit protective T cell immunity.This work was supported by the Portuguese Foundation for Science and Technology individual fellowship (CNA) www.fct.pt, a National Institutes of Health Grant R01 AI106725 (SMB) www.nih.gov, and a Center for AIDS Research Grant P30 AI 060354 (SMB) www.nih.gov. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Biomass of fine roots in different land cover types at the "arc of deforestation", Brazil

This study aims to evaluate the effect of land cover type, soil properties, and vegetation structure on fine root biomass, and examined how these factors affect diameter of fine roots. The study was conducted in communities located in the Nova Ipixuna, Parauapebas and Pacajá municipalities of Pará state. In each area, nine farms were selected; in each farm were sampled five plots, totaling 135 plots distributed into nine different types of land cover; at each plot, four soil samples were collected to quantify the fine roots, vegetation cover was inventoried, and soil was collected for physical and chemical characterization. Fine roots were separated into four different classes. Principal Component Analysis (PCA) were done for the soil and vegetation matrix and they were compared with the fine root biomass PCA through a co-inertia analysis. Variability was high for fine root biomass data. All land covers exhibited a high proportion of fine roots > 1 mm. The co- inertia analysis showed that the fine root biomass PCA share a common structure with vegetation PCA, with 37/100 of the variability being explained; however only 9/100 of the variability was explained by the soil PCA. Our results highlight the importance of roots with diameters 2 mm was critical to the differentiation among land covers

Mycoplasmosis in Ferrets

We report an outbreak of severe respiratory disease associated with a novel Mycoplasma species in ferrets. During 2009–2012, a respiratory disease characterized by nonproductive coughing affected ≈8,000 ferrets, 6–8 weeks of age, which had been imported from a breeding facility in Canada. Almost 95% became ill, but almost none died. Treatments temporarily decreased all clinical signs except cough. Postmortem examinations of euthanized ferrets revealed bronchointerstitial pneumonia with prominent hyperplasia of bronchiole-associated lymphoid tissue. Immunohistochemical analysis with polyclonal antibody against Mycoplasma bovis demonstrated intense staining along the bronchiolar brush border. Bronchoalveolar lavage samples from 12 affected ferrets yielded fast-growing, glucose-fermenting mycoplasmas. Nucleic acid sequence analysis of PCR-derived amplicons from portions of the 16S rDNA and RNA polymerase B genes failed to identify the mycoplasmas but showed that they were most similar to M. molare and M. lagogenitalium. These findings indicate a causal association between the novel Mycoplasma species and the newly recognized pulmonary disease

H i in group interactions: HCG 44

Extending deep observations of the neutral atomic hydrogen (HI) to the environment around galaxy groups can reveal a complex history of group interactions which is invisible to studies that focus on the stellar component. Hickson Compact Group 44 (HCG 44) is a nearby example and we have combined HI data from the Karoo Array Telescope, Westerbork Synthesis Radio Telescope, and Arecibo Legacy Fast ALFA survey, in order to achieve high column density sensitivity (N_HI < 2x10^18 cm^-2) to the neutral gas over a large field-of-view beyond the compact group itself. We find the giant HI tail north of HCG 44 contains 1.1x10^9 M_Sun of gas and extends 450 kpc from the compact group: twice as much mass and 33% further than previously detected. However, the additional gas is still unable to account for the known HI deficiency of HCG 44. The tail likely formed through a strong tidal interaction and HI clouds in the tail have survived for 1 Gyr or more after being stripped. This has important implications for understanding the survival of neutral clouds in the intragroup and circumgroup medium, and we discuss their survival in the context of simulations of cold gas in hot halos. HCG 44 is one of a growing number of galaxy groups found to have more extended HI in the intragroup and circumgroup medium than previously measured. Our results provide constraints for simulations on the properties of galaxy group halos, and reveal a glimpse of what will be seen by future powerful HI telescopes and surveys.Comment: 12 pages, 6 figures. Accepted for publication in MNRA

Biofonctionnements des sols tropicaux et mode de gestion des terres

En Amazonie brésilienne, la presque totalité des zones déforestées depuis une trentaine d'années a servi à l'installation de pâturages dont une moitié a été depuis abandonnée dans un état de dégradation souvent avancé. Plusieurs hypothèses ont été émises pour expliquer cette dégradation, parmi lesquelles la détérioration de certaines propriétés physiques et chimiques des sols, le développement incontrôlé des adventices, l'effet des changements des peuplements de la macrofaune du sol, les attaques parasitaires, les effets de la gestion des parcelles. Afin de vérifier ces hypothèses, une étude comparative de plusieurs pâturages a été réalisée, associant leur historique, l'analyse de leur végétation (graminée plantée et végétation secondaire), de leur macrofaune et de quelques propriétés des sols. Deux groupes de pâturages ont été sélectionnés en fonction de leur état apparent de dégradation, sur des Oxisols en Amazonie centrale et des Ultisols en Amazonie orientale. La dégradation des pâturages, caractérisée par une diminution de la phytomasse de la graminée introduite et l'augmentation de celle des adventices, n'apparaît directement liée à l'âge du pâturage ni à une dégradation marquée des sols. La déforestation et le brûlis qui la suivent provoquent généralement un tassement des horizons superficiels, une augmentation du pH, de la somme des bases et du taux de saturation. Au cours des années qui suivent l'installation du pâturage, ces caractéristiques évoluent très peu, indépendamment de l'état de dégradation des pâturages. La quantité de phosphore extractible et les teneurs en carbone organique et azote total n'évoluent pas de façon sensible en fonction de l'âge et de la dégradation des pâturages. Les peuplements de la macrofaune du sol sont en général fortement modifiés par la mise en pâturage... (D'après résumé d'auteur

Retrogenic T cell priming and acquisition of effector functions.

<p>(<b>a</b>) Kinetic analysis of frequency (filled circles) and number (opened circles) of activated (CD44^HiCD62L^Lo) Rg cells in the draining LN (left panel) and lung (right panel) following adoptive transfer into mice infected with <i>M</i>. <i>tuberculosis</i>. (<b>b</b>) Kinetic analysis of frequency of divided Rg cells in the draining LN, lung and spleen following adoptive transfer into mice infected with <i>M</i>. <i>tuberculosis</i>. (<b>c</b>) Kinetic analysis of frequency of IFNγ-producing Rg cells in the draining LN (left panel) and lung (right panel) following adoptive transfer into mice infected with <i>M</i>. <i>tuberculosis</i>. Data are representative from two (b) or three (a, c) independent experiments, each with 5 mice per group. (<b>a,c</b>) One way ANOVA with Dunnett’s post test to compare differences over time (vs. day 7 [<b>a</b>] or d11 [<b>c</b>]) time points. P<0.05 indicated by asterisks (phenotype or IFNγ) or hash marks (cell numbers). (<b>b</b>) One way ANOVA with Tukey’s post test to compare differences in proliferation between lung, LN and spleen; p<0.05 indicated by asterisks.</p

Anti-TCR antibodies and their specificity.

<p>Anti-TCR antibodies and their specificity.</p