Comparative Gamma Delta T Cell Immunology: A Focus on Mycobacterial Disease in Cattle

A theme among many pathogenic mycobacterial species affecting both humans and animals is a prolonged asymptomatic or latent period that can last years to decades. The mechanisms that favor progression to active disease are not well understood. Pathogen containment is often associated with an effective cell-mediated or T-helper 1 immune profile. With certain pathogenic mycobacteria, such as Mycobacterium avium subspecies paratuberculosis, a shift to active clinical disease is associated with loss of T-helper 1 immunity and development of an ineffective humoral or T-helper 2 immune response. Recently γδ T cells have been shown to play a role early in mycobacterial infections and have been hypothesized to influence disease outcome. The purpose of this paper is to compare recent advancements in our understanding of γδ T cells in humans, cattle, and mice and to discuss roles of γδ T cells in host response to mycobacterial infection

Inoculation of Weaned Pigs by Feed, Water, and Airborne Transmission of Salmonella enterica Serotype 4,[5],12:i:-

Salmonella enterica serotype 4,[5],12:i:- (STM) has become an increasing problem for food safety and has been often detected in pork products. For this study, weanling pigs were exposed to STM-contaminated feed, water, or air to determine possible STM transmission routes. An uninoculated control group of pigs was included. The STM was monitored daily in feces and rectal and nasal swabs. The STM colonization was most prevalent in tissues from tonsil, lower intestine, and mesenteric lymph nodes. No differences in lesion severity were observed between inoculated and control pigs. Contaminated feed, water, and aerosolized particles caused infection in weaned pigs; however, no STM colonization was observed in skeletal muscle destined for human consumption. Based on the results from this study, STM contamination in pork products most likely results from cross-contamination of meat by digesta or lymph node tissue during processing

Inoculation of Weaned Pigs by Feed, Water, and Airborne Transmission of Salmonella enterica Serotype 4,[5],12:i:-

Salmonella enterica serotype 4,[5],12:i:- (STM) has become an increasing problem for food safety and has been often detected in pork products. For this study, weanling pigs were exposed to STM-contaminated feed, water, or air to determine possible STM transmission routes. An uninoculated control group of pigs was included. The STM was monitored daily in feces and rectal and nasal swabs. The STM colonization was most prevalent in tissues from tonsil, lower intestine, and mesenteric lymph nodes. No differences in lesion severity were observed between inoculated and control pigs. Contaminated feed, water, and aerosolized particles caused infection in weaned pigs; however, no STM colonization was observed in skeletal muscle destined for human consumption. Based on the results from this study, STM contamination in pork products most likely results from cross-contamination of meat by digesta or lymph node tissue during processing

Exposure to mild blast forces induces neuropathological effects, neurophysiological deficits and biochemical changes

Direct or indirect exposure to an explosion can induce traumatic brain injury (TBI) of various severity levels. Primary TBI from blast exposure is commonly characterized by internal injuries, such as vascular damage, neuronal injury, and contusion, without external injuries. Current animal models of blast-induced TBI (bTBI) have helped to understand the deleterious effects of moderate to severe blast forces. However, the neurological effects of mild blast forces remain poorly characterized. Here, we investigated the effects caused by mild blast forces combining neuropathological, histological, biochemical and neurophysiological analysis. For this purpose, we employed a rodent blast TBI model with blast forces below the level that causes macroscopic neuropathological changes. We found that mild blast forces induced neuroinflammation in cerebral cortex, striatum and hippocampus. Moreover, mild blast triggered microvascular damage and axonal injury. Furthermore, mild blast caused deficits in hippocampal short-term plasticity and synaptic excitability, but no impairments in long-term potentiation. Finally, mild blast exposure induced proteolytic cleavage of spectrin and the cyclin-dependent kinase 5 activator, p35 in hippocampus. Together, these findings show that mild blast forces can cause aberrant neurological changes that critically impact neuronal functions. These results are consistent with the idea that mild blast forces may induce subclinical pathophysiological changes that may contribute to neurological and psychiatric disorders

Bovine WC1+ and WC1neg γδ T Lymphocytes Influence Monocyte Differentiation and Monocyte-Derived Dendritic Cell Maturation during In Vitro Mycobacterium avium Subspecies paratuberculosis Infection

During early Mycobacterium avium subspecies paratuberculosis (Map) infection, complex interactions occur between the bacteria, cells from the mononuclear phagocyte system (MPS) including both resident (macrophages and dendritic cells) and recruited (monocytes) cells, and other mucosal sentinel cells such as γδ T lymphocytes. Though the details of early host–pathogen interactions in cattle remain largely underexplored, our hypothesis is that these significantly influence development of host immunity and ultimate success or failure of the host to respond to Map infection. The aims of the present study were to first characterize monocyte-derived MPS cells from young calves with respect to their immunophenotype and function. Then, we set out to investigate the effects of WC1+ and WC1neg γδ T lymphocytes on (1) the differentiation of autologous monocytes and (2) the maturation of autologous monocyte-derived dendritic cells (MDDCs). To achieve this, peripheral blood WC1+ or WC1neg γδ T lymphocytes were cocultured with either autologous freshly isolated peripheral blood-derived monocytes or autologous immature MDDCs (iMDDCs). We began by measuring several markers of interest on MPS cells. Useful markers to distinguish monocyte-derived macrophages (MDMs) from MDDCs include CD11b, CD163, and CD172a, which are expressed significantly higher on MDMs compared with MDDCs. Function, but not phenotype, was influenced by WC1neg γδ T lymphocytes: viability of Map harvested from monocytes differentiated in the presence of WC1neg γδ T lymphocytes (dMonWC1neg) was significantly lower compared to MDMs and MDDCs. With respect to DC maturation, we first showed that mature MDDCs (mMDDCs) have significantly higher expression of CD11c, CD80, and CD86 compared with iMDDCs, and the phagocytic capacity of mMDDCs is significantly reduced compared to iMDDCs. We then showed that γδ T lymphocyte subsets induce functional (reduced phagocytosis) but not phenotypic (surface marker expression) iMDDC maturation. These data collectively show that γδ T lymphocytes influence differentiation, maturation, and ultimately the function of monocytes during Map infection, which has significant implications on survival of Map and success of host defense during early Map infection

Resilience to infection by Mycobacterium avium subspecies paratuberculosis following direct intestinal inoculation in calves

Abstract Mycobacterium avium subspecies paratuberculosis (Map) is the cause of Johne’s disease, a chronic enteritis of cattle. A significant knowledge gap is how persistence of Map within the intestinal tract after infection contributes to progression of disease. To address this, we exposed calves to Map by direct ileocecal Peyer’s patch injection. Our objective was to characterize the persistence of Map in tissues, associated intestinal lesions, fecal Map shedding, and serum antibody responses, through the first 28-weeks post-inoculation (wpi). Previous work using this model showed 100% rate of Map infection in intestine and lymph node by 12 wpi. We hypothesized that direct inoculation of Map into the distal small intestine would induce intestinal Map infection with local persistence and progression towards clinical disease. However, our data show decreased persistence of Map in the distal small intestine and draining lymph nodes. We identified Map in multiple sections of distal ileum and draining lymph node of all calves at 4 and 12 wpi, but then we observed reduced Map in distal ileum at 20 wpi, and by 28 wpi we found that 50% of animals had no detectable Map in intestine or the lymph node. This provides evidence of resilience to Map infection following direct intestinal Map inoculation. Further work examining the immune responses and host–pathogen interactions associated with this infection model are needed to help elicit the mechanisms underlying resilience to Map infection

Directional microwave ablation in spine: experimental assessment of computational modeling

AbstractBackground Despite the theoretical advantages of treating metastatic bone disease with microwave ablation (MWA), there are few reports characterizing microwave absorption and bioheat transfer in bone. This report describes a computational modeling-based approach to simulate directional microwave ablation (dMWA) in spine, supported by ex vivo and pilot in vivo experiments in porcine vertebral bodies.Materials and methods A 3D computational model of microwave ablation within porcine vertebral bodies was developed. Ex vivo porcine vertebra experiments using a dMWA applicator measured temperatures approximately 10.1 mm radially from the applicator in the direction of MW radiation (T1) and approximately 2.4 mm in the contra-lateral direction (T2). Histologic assessment of ablated ex vivo tissue was conducted and experimental results compared to simulations. Pilot in vivo experiments in porcine vertebral bodies assessed ablation zones histologically and with CT and MRI.Results Experimental T1 and T2 temperatures were within 3–7% and 11–33% of simulated temperature values. Visible ablation zones, as indicated by grayed tissue, were smaller than those typical in other soft tissues. Posthumous MRI images of in vivo ablations showed hyperintensity. In vivo experiments illustrated the technical feasibility of creating directional microwave ablation zones in porcine vertebral body.Conclusion Computational models and experimental studies illustrate the feasibility of controlled dMWA in bone tissue