Time to understand a cluttered spatial scene.

When searching for people in collapsed buildings, Urban Search and Rescue workers need to comprehend a complex cluttered scene observed through an endoscope under time pressure. This paper addresses the effects of time pressure and spatial ability on the comprehension of a flm showing a mock-up collapsed room that was explored using endoscope-like technology. Participants' task was to find the objects that were hidden in the rubble, describe where they had found them, and draw the scene. Analysis focused on coherence and spatial specificity. Results indicate that spatial skills were most decisive for understanding and conceptually integrating the scene. Time pressure only affected the amount of objects found, not the degree of conceptual integration as re ected in the descriptions

Macrophage origin limits functional plasticity in helminth-bacterial co-infection

Rapid reprogramming of the macrophage activation phenotype is considered important in the defense against consecutive infection with diverse infectious agents. However, in the setting of persistent, chronic infection the functional importance of macrophage-intrinsic adaptation to changing environments vs. recruitment of new macrophages remains unclear. Here we show that resident peritoneal macrophages expanded by infection with the nematode Heligmosomoides polygyrus bakeri altered their activation phenotype in response to infection with Salmonella enterica ser. Typhimurium in vitro and in vivo. The nematode-expanded resident F4/80high macrophages efficiently upregulated bacterial induced effector molecules (e.g. MHC-II, NOS2) similarly to newly recruited monocyte-derived macrophages. Nonetheless, recruitment of blood monocyte-derived macrophages to Salmonella infection occurred with equal magnitude in co-infected animals and caused displacement of the nematode-expanded, tissue resident-derived macrophages from the peritoneal cavity. Global gene expression analysis revealed that although nematode-expanded resident F4/80high macrophages made an anti-bacterial response, this was muted as compared to newly recruited F4/80low macrophages. However, the F4/80high macrophages adopted unique functional characteristics that included enhanced neutrophil-stimulating chemokine production. Thus, our data provide important evidence that plastic adaptation of MΦ activation does occur in vivo, but that cellular plasticity is outweighed by functional capabilities specific to the tissue origin of the cell

Diversity, host specialization, and geographic structure of filarial nematodes infecting Malagasy bats

We investigated filarial infection in Malagasy bats to gain insights into the diversity of these parasites and explore the factors shaping their distribution. Samples were obtained from 947 individual bats collected from 52 sites on Madagascar and representing 31 of the 44 species currently recognized on the island. Samples were screened for the presence of micro-and macro-parasites through both molecular and morphological approaches. Phylogenetic analyses showed that filarial diversity in Malagasy bats formed three main groups, the most common represented by Litomosa spp. infecting Miniopterus spp. (Miniopteridae); a second group infecting Pipistrellus cf. hesperidus (Vespertilionidae) embedded within the Litomosoides cluster, which is recognized herein for the first time from Madagascar; and a third group composed of lineages with no clear genetic relationship to both previously described filarial nematodes and found in M. griveaudi, Myotis goudoti, Neoromicia matroka (Vespertilionidae), Otomops madagascariensis (Molossidae), and Paratriaenops furculus (Hipposideridae). We further analyzed the infection rates and distribution pattern of Litomosa spp., which was the most diverse and prevalent filarial taxon in our sample. Filarial infection was disproportionally more common in males than females in Miniopterus spp., which might be explained by some aspect of roosting behavior of these cave-dwelling bats. We also found marked geographic structure in the three Litomosa clades, mainly linked to bioclimatic conditions rather than host-parasite associations. While this study demonstrates distinct patterns of filarial nematode infection in Malagasy bats and highlights potential drivers of associated geographic distributions, future work should focus on their alpha taxonomy and characterize arthropod vectors

CCL17 exerts a neuroimmune modulatory function and is expressed in hippocampal neurons

Chemokines are important signaling molecules in the immune and nervous system. Using a fluorescence reporter mouse model, we demonstrate that the chemokine CCL17, a ligand of the chemokine receptor CCR4, is produced in the murine brain, particularly in a subset of hippocampal CA1 neurons. We found that basal expression of Ccl17 in hippocampal neurons was strongly enhanced by peripheral challenge with lipopolysaccharide (LPS). LPS-mediated induction of Ccl17 in the hippocampus was dependent on local tumor necrosis factor (TNF) signaling, whereas upregulation of Ccl22 required granulocyte-macrophage colony-stimulating factor (GM-CSF). CCL17 deficiency resulted in a diminished microglia density under homeostatic and inflammatory conditions. Further, microglia from naive Ccl17-deficient mice possessed a reduced cellular volume and a more polarized process tree as assessed by computer-assisted imaging analysis. Regarding the overall branching, cell surface area, and total tree length, the morphology of microglia from naive Ccl17-deficient mice resembled that of microglia from wild-type mice after LPS stimulation. In line, electrophysiological recordings indicated that CCL17 downmodulates basal synaptic transmission at CA3-CA1 Schaffer collaterals in acute slices from naive but not LPS-treated animals. Taken together, our data identify CCL17 as a homeostatic and inducible neuromodulatory chemokine affecting the presence and morphology of microglia and synaptic transmission in the hippocampus

Anti-bacterial effector mechanisms are enhanced by <i>L. sigmodontis</i> infection in a TLR2 dependent manner.

<p>(<b>A</b>) Colony forming units (cfu) obtained by a gentamycin assay using peritoneal macrophages derived from chronic <i>L. sigmodontis</i> (<i>L.s.</i>)-infected wild type and TLR2^-/- mice and respective uninfected controls three hours after i.p. <i>E. coli</i> injection. (<b>B</b>) Nitrite concentrations of the same macrophages as in (<b>A</b>) after ex vivo cultivation for 48 hours. Frequency of peritoneal F4/80^-positive macrophages from <i>L.s.-</i>infected and uninfected wild type and TLR2^-/- mice (n = 5 per group) that phagocytosed pHrodo <i>E. coli</i>-BioParticles 90 minutes post injection (<b>C</b>) or from <i>L.s.</i>-infected and uninfected wild type mice (n = 5 per group) that phagocytosed pHrodo <i>S. aureus</i>-BioParticles three hours post injection (<b>D</b>). (<b>A</b>) Pooled data from two independent experiments with at least four mice per group. Data shown in (<b>A-C</b>) is illustrated as mean + SEM and was tested for statistical significance by 1-way ANOVA followed by Dunn’s multiple comparisons test; Data in (<b>D</b>) is also shown as mean + SEM and was tested for statistical significance by Mann-Whitney U test. *p< 0.05; **p< 0.01; ***p<0.001.</p

Chronic Filarial Infection Provides Protection against Bacterial Sepsis by Functionally Reprogramming Macrophages

<div><p>Helminths immunomodulate their hosts and induce a regulatory, anti-inflammatory milieu that prevents allergies and autoimmune diseases. Helminth immunomodulation may benefit sepsis outcome by preventing exacerbated inflammation and severe pathology, but the influence on bacterial clearance remains unclear. To address this, mice were chronically infected with the filarial nematode <i>Litomosoides sigmodontis (L.s.)</i> and the outcome of acute systemic inflammation caused by i.p. <i>Escherichia coli</i> injection was determined. L.s. infection significantly improved <i>E. coli</i>-induced hypothermia, bacterial clearance and sepsis survival and correlated with reduced concentrations of associated pro-inflammatory cytokines/chemokines and a less pronounced pro-inflammatory macrophage gene expression profile. Improved sepsis outcome in <i>L.s.</i>-infected animals was mediated by macrophages, but independent of the alternatively activated macrophage subset. Endosymbiotic Wolbachia bacteria that are present in most human pathogenic filariae, as well as <i>L.s.</i>, signal via TLR2 and modulate macrophage function. Here, gene expression profiles of peritoneal macrophages from <i>L.s.</i>-infected mice revealed a downregulation of genes involved in TLR signaling, and pulsing of macrophages in vitro with <i>L.s.</i> extract reduced LPS-triggered activation. Subsequent transfer improved sepsis outcome in naïve mice in a <i>Wolbachia</i>- and TLR2-dependent manner. In vivo, phagocytosis was increased in macrophages from <i>L.s.</i>-infected wild type, but not TLR2-deficient animals. In association, <i>L.s.</i> infection neither improved bacterial clearance in TLR2-deficient animals nor ameliorated <i>E. coli</i>-induced hypothermia and sepsis survival. These results indicate that chronic <i>L.s.</i> infection has a dual beneficial effect on bacterial sepsis, reducing pro-inflammatory immune responses and improving bacterial control. Thus, helminths and their antigens may not only improve the outcome of autoimmune and allergic diseases, but may also present new therapeutic approaches for acute inflammatory diseases that do not impair bacterial control.</p></div

Anti-bacterial effector mechanisms are enhanced by <i>L. sigmodontis</i> infection in a TLR2 dependent manner.

<p>(<b>A</b>) Colony forming units (cfu) obtained by a gentamycin assay using peritoneal macrophages derived from chronic <i>L. sigmodontis</i> (<i>L.s.</i>)-infected wild type and TLR2^-/- mice and respective uninfected controls three hours after i.p. <i>E. coli</i> injection. (<b>B</b>) Nitrite concentrations of the same macrophages as in (<b>A</b>) after ex vivo cultivation for 48 hours. Frequency of peritoneal F4/80^-positive macrophages from <i>L.s.-</i>infected and uninfected wild type and TLR2^-/- mice (n = 5 per group) that phagocytosed pHrodo <i>E. coli</i>-BioParticles 90 minutes post injection (<b>C</b>) or from <i>L.s.</i>-infected and uninfected wild type mice (n = 5 per group) that phagocytosed pHrodo <i>S. aureus</i>-BioParticles three hours post injection (<b>D</b>). (<b>A</b>) Pooled data from two independent experiments with at least four mice per group. Data shown in (<b>A-C</b>) is illustrated as mean + SEM and was tested for statistical significance by 1-way ANOVA followed by Dunn’s multiple comparisons test; Data in (<b>D</b>) is also shown as mean + SEM and was tested for statistical significance by Mann-Whitney U test. *p< 0.05; **p< 0.01; ***p<0.001.</p