Apoptotic cell clearance of Leishmania major-infected neutrophils by dendritic cells inhibits CD8⁺ T-cell priming in vitro by Mer tyrosine kinase-dependent signaling.

Neutrophils are the predominant recruited and infected cells during the early stages of Leishmania major infection in the skin, and depletion of neutrophils promotes immunity to infection transmitted by sand fly bite. In order to better understand how the acute neutrophilic response suppresses immunity, we assessed the consequences of the interaction between neutrophils recovered from the skin-inoculation site and bone marrow-derived dendritic cells (DCs) in vitro. The capture of infected, apoptotic neutrophils by the DCs completely inhibited their cross-presentation function that was dependent on engagement of the receptor tyrosine kinase Mer on the DCs. The capture of uninfected neutrophils, or neutrophils infected with Toxoplasma gondii, had only slight immunomodulatory effects. These studies define the clearance of infected, apoptotic neutrophils by DCs and Mer receptor signaling as central to the early immune evasion strategies of L. major, with relevance to other vector-borne pathogens delivered by bite to the skin.

Neutrophils, apoptosis and phagocytic clearance: an innate sequence of cellular responses regulating intramacrophagic parasite infections.

In complex organisms, apoptosis is a constitutive cell death process that is involved in physiological regulation of cell numbers and that can also be induced in the course of inflammatory and immune responses. Neutrophils are among the first cells recruited during inflammation. Neutrophils constitutively die by apoptosis at inflamed sites, and are ingested by macrophages. Recent studies investigated how phagocytic clearance of senescent neutrophils influences the survival of intracellular protozoan parasites that have been phagocytosed by, or have invaded phagocytes. The results indicate that neutrophil clearance plays an unexpected role in regulation of intramacrophagic protozoan parasite infection.

Density, proportion, and dendritic coverage of retinal ganglion cells of the common marmoset (Callithrix jacchus jacchus).

We performed a quantitative analysis of M and P cell mosaics of the common-marmoset retina. Ganglion cells were labeled retrogradely from optic nerve deposits of Biocytin. The labeling was visualized using horseradish peroxidase (HRP) histochemistry and 3-3'diaminobenzidine as chromogen. M and P cells were morphologically similar to those found in Old- and New-World primates. Measurements were performed on well-stained cells from 4 retinas of different animals. We analyzed separate mosaics for inner and outer M and P cells at increasing distances from the fovea (2.5-9 mm of eccentricity) to estimate cell density, proportion, and dendritic coverage. M cell density decreased towards the retinal periphery in all quadrants. M cell density was higher in the nasal quadrant than in other retinal regions at similar eccentricities, reaching about 740 cells/mm(2) at 2.5 mm of temporal eccentricity, and representing 8-14% of all ganglion cells. P cell density increased from peripheral to more central regions, reaching about 5540 cells/mm(2) at 2.5 mm of temporal eccentricity. P cells represented a smaller proportion of all ganglion cells in the nasal quadrant than in other quadrants, and their numbers increased towards central retinal regions. The M cell coverage factor ranged from 5 to 12 and the P cell coverage factor ranged from 1 to 3 in the nasal quadrant and from 5 to 12 in the other quadrants. These results show that central and peripheral retinal regions differ in terms of cell class proportions and dendritic coverage, and their properties do not result from simply scaling down cell density. Therefore, differences in functional properties between central and peripheral vision should take these distinct regional retinal characteristics into account.

Density, proportion, and dendritic coverage of retinal ganglion cells of the common marmoset (Callithrix jacchus jacchus)

We performed a quantitative analysis of M and P cell mosaics of the common-marmoset retina. Ganglion cells were labeled retrogradely from optic nerve deposits of Biocytin. The labeling was visualized using horseradish peroxidase (HRP) histochemistry and 3-3'diaminobenzidine as chromogen. M and P cells were morphologically similar to those found in Old- and New-World primates. Measurements were performed on well-stained cells from 4 retinas of different animals. We analyzed separate mosaics for inner and outer M and P cells at increasing distances from the fovea (2.5-9 mm of eccentricity) to estimate cell density, proportion, and dendritic coverage. M cell density decreased towards the retinal periphery in all quadrants. M cell density was higher in the nasal quadrant than in other retinal regions at similar eccentricities, reaching about 740 cells/mm² at 2.5 mm of temporal eccentricity, and representing 8-14 percent of all ganglion cells. P cell density increased from peripheral to more central regions, reaching about 5540 cells/mm² at 2.5 mm of temporal eccentricity. P cells represented a smaller proportion of all ganglion cells in the nasal quadrant than in other quadrants, and their numbers increased towards central retinal regions. The M cell coverage factor ranged from 5 to 12 and the P cell coverage factor ranged from 1 to 3 in the nasal quadrant and from 5 to 12 in the other quadrants. These results show that central and peripheral retinal regions differ in terms of cell class proportions and dendritic coverage, and their properties do not result from simply scaling down cell density. Therefore, differences in functional properties between central and peripheral vision should take these distinct regional retinal characteristics into account.

Human monocytes and monocyte-derived macrophage phagocytosis of serotype III group B streptococci strains.

In this report group B streptococci (GBS) strains 90356 and 80340 isolated from liquor and vagina, respectively, were placed into contact with human peripheral blood monocytes (PBM) and macrophages derived from monocytes (MDM) by differentiation in vitro. The increased expression of CD16 and CD68 by macrophages cultured for 7 days compared with adherent monocytes supported the distinct maturation status of these cells. The number of viable intracellular bacteria of the 90356 strain was observed after 2 h of incubation with PBM (P < 0.001) and 0.5 h with MDM (P < 0.001). MDM cells seemed to present a more efficient mechanism of bacterial destruction of GBS type III, isolated from a case of meningitis. Viable cells of strain 80340, isolated from the vagina, were not detected in significant numbers in PBM and MDM phagocytic cells. These findings add to our current understanding of the roles played by multiple receptor-ligand systems in the uptake and pathogenesis of group B streptococci infection. Survival strategies of GBS, which interfere with macrophage bactericidal functions, might exist.

Ganglion cells of a short-wavelength-sensitive cone pathway in New World monkeys: morphology and physiology.

We have studied the morphology and physiology of retinal ganglion cells of a short-wavelength-sensitive cone (SWS-cone) pathway in dichromatic and trichromatic New World anthropoids, the capuchin monkey (Cebus apella) and tufted-ear marmoset (Callithrix jacchus). In Old World anthropoids, in which males and females are both trichromats, blue-ON/yellow-OFF retinal ganglion cells have excitatory SWS-cone and inhibitory middle- and long-wavelength-sensitive (MWS- and LWS-) cone inputs, and have been anatomically identified as small-field bistratified ganglion cells (SB-cells) (Dacey & Lee, 1994). Among retinal ganglion cells of New World monkeys, we find SB-cells which have very similar morphology to such cells in macaque and human; for example, the inner dendritic tree is larger and denser than the outer dendritic tree. We also find blue-on retinal ganglion cells of the capuchin to have physiological responses strongly resembling such cells of the macaque monkey retina; for example, responses were more sustained, with a gentler low frequency roll-off than MC-cells, and no evidence of contrast gain control. There was no difference between dichromatic and trichromatic individuals. The results support the view that SWS-cone pathways are similarly organized in New and Old World primates, consistent with the hypothesis that these pathways form a phylogenetically ancient color system.

The retinal ganglion cell classes of New World primates.

In the primate retina there are distinct ganglion cell classes, exhibiting particular morphologies and central projections, each responsible for conveying particular types of visual information to the brain. The chief retinal inputs to the cortex arise from specific ganglion cell classes, M-ganglion cells, responsible for carrying the luminance signal, and P-ganglion cells, that convey the red-green color opponent signal, as well as high contrast luminance signal. There are other ganglion cell classes, such as small-field bistratified cells, exhibiting dendrites that stratify at two different levels in the inner plexiform layer, which convey the blue-yellow color opponent signal. Most published data concerning primate retinal ganglion cell anatomy and physiology have been obtained from Old World species. Studies on New World monkeys have recently become of interest since they differ from the Old World monkeys with respect to the color vision inheritance pattern. On reviewing retinal ganglion cell layer organization in New World monkeys, it seems that there are more similarities than differences in relation to the Old World monkeys. Diurnal genera of New World monkeys exhibit a well-developed fovea centralis and ganglion cell density peak, as well as peripheral density values which are in the range reported for Old World monkeys and human. Moreover, all the major ganglion cell classes identified in Old World monkeys are also present in New World primates. Up to now, no obvious anatomical differences between dichromats and trichromats have been reported. The only genus that is significantly different from the others is the Aotus. It exhibits lower ganglion cell density in the central retina, and apparently lacks the small-field bistratified cells.