Leukotriene B4 receptor BLT1 signaling is critical for neutrophil apoptosis and resolution of experimental Lyme arthritis.

Eicosanoids are powerful mediators of inflammation and are known to drive both the progression and regression of arthritis. We previously reported the infection of C3H 5-lipoxygenase (LO)-deficient mice with Borrelia burgdorferi results in prolonged nonresolving Lyme arthritis. Here we define the role of the 5-LO metabolite leukotriene (LT)B4 and its high-affinity receptor, BLT1, in this response. C3H and C3H BLT1-/- mice were infected with B. burgdorferi and arthritis progression was monitored by ankle swelling over time. Similar to 5-LO-/- mice, BLT1-/- mice developed nonresolving Lyme arthritis characterized by increased neutrophils in the joint at later time points than WT mice, but with fewer apoptotic (caspase-3+ ) neutrophils. In vitro, BLT1-/- neutrophils were defective in their ability to undergo apoptosis due to the lack of LTB4 -mediated down-regulation of cAMP, subsequent failure to induce Death-Inducing Signaling Complex (DISC) components, and decreased FasL and CD36 expression. Inhibition of adenylyl cyclase with SQ 22,536 restored BLT1-/- BMN apoptosis, FasL and CD36 expression, and clearance by macrophages. We conclude that LTB4/BLT1 signaling has an unexpected critical role in mediating neutrophil apoptosis via the down-regulation of cAMP. Loss of BLT1 signaling led to defective clearance of neutrophils from the inflamed joint and failed arthritis resolution.

Treatment of Borrelia burgdorferi-Infected Mice with Apoptotic Cells Attenuates Lyme Arthritis via PPAR-γ.

Infection of mice with Borrelia burgdorferi causes an inflammatory arthritis that peaks 3-4 wk postinfection and then spontaneously resolves. Although the recruitment of neutrophils is known to drive the development of arthritis, mechanisms of disease resolution remain unclear. Efficient clearance of apoptotic cells (AC) is likely an important component of arthritis resolution. In this article, we show the number of AC increases in the joints of B. burgdorferi-infected mice around day 21 postinfection and peaks around day 28. Injection of AC directly into the ankles of B. burgdorferi-infected mice limited ankle swelling but had no effect on spirochete clearance or arthritis severity scores. In vitro, addition of AC to bone marrow macrophage cultures decreased B. burgdorferi-induced TNF-α and KC and increased IL-10. In addition, phagocytosis of B. burgdorferi and neutrophil migration to LTB4 were inhibited by AC. Exogenous AC caused an increase in peroxisome proliferator-activated receptor-γ (PPAR-γ) expression both in vitro and in vivo during B. burgdorferi infection. The PPAR-γ agonist rosiglitazone elicited similar changes in macrophage cytokine production and neutrophil migration as exogenous AC. Addition of the PPAR-γ antagonist GW 9662 abrogated the effects of AC in vitro. Injection of rosiglitazone directly into the tibiotarsal joints of B. burgdorferi-infected mice decreased ankle swelling and immune cell recruitment, similar to the injection of AC. These results suggest that clearance of AC plays a role in the resolution of inflammation during experimental Lyme arthritis through the activation of PPAR-γ. PPAR-γ agonists, such as rosiglitazone, may therefore be effective treatments for inducing arthritis resolution.

Correction to: Transcriptome profiling of resistance response to Meloidogyne chitwoodi introgressed from wild species Solanum bulbocastanum into cultivated potato.

Following the publication of this article [1], the authors noted an error in Figure 11.

Smaller brained cliff swallows are more likely to die during harsh weather.

The cognitive-buffer hypothesis proposes that more harsh and unpredictable environments favour animals with larger brains and resulting greater cognitive skills. Comparisons across taxa have supported the hypothesis, but it has rarely been tested within a species. We measured brain size, as inferred from head dimensions, for 1141 cliff swallow specimens collected in western Nebraska, 1982-2018. Cliff swallows starving to death during unusual late-spring cold snaps had significantly smaller brains than those dying from other causes, suggesting that brain size in this species can affect foraging success and that greater cognitive ability may confer advantages when conditions exceed normal environmental extremes. Brain size declined significantly with the size of the breeding colony from which a specimen came. Larger brains may be favoured in smaller colonies that represent more unpredictable and more challenging social environments where there is less public information on food sources and less collective vigilance against predators, even in relatively normal conditions. Our results provide intraspecific support for the cognitive-buffer hypothesis and emphasize the potential evolutionary impact of rare climatic events.

Elimination of Tobacco rattle virus from viruliferous Paratrichodorus allius in greenhouse pot experiments through cultivation of castle russet.

Corky ringspot (CRS) is a widespread potato tuber necrotic disease caused by Tobacco rattle virus (TRV) infection. In the Pacific Northwest, this virus is transmitted by the stubby root nematode (SRN) within the genus Paratrichodorus. Remediating CRS affected fields is a major challenge that can be mitigated by growing plant varieties that are resistant to TRV infection. Growing alfalfa has been shown to reduce TRV levels in CRS infested fields over time but the development of a potato cultivar with these same capabilities would be of great economic benefit to potato growers. Castle Russet is a new potato clone that does not develop symptoms of CRS disease. To assess its ability to reduce soil virus load, Castle Russet, tobacco var. "Samsun NN", alfalfa var. "Vernema", and Russet Burbank potato were grown for a period of 1 to 3 months in soils containing viruliferous SRN populations at two different inoculation pressures (60 nematodes/pot and 1060 nematodes/pot) in greenhouse pot experiments. SRN population size and the presence of TRV were assessed over several months post inoculation. Results indicate that plant host and length of exposure significantly influence SRN population dynamics, whereas the TRV infection status of bait plants was significantly affected by both of these factors as well as inoculation pressure. These results suggest that both alfalfa var. "Vernema" and Castle Russet are resistant to TRV infection and may potentially be used to eliminate the virus from fields affected by CRS.Corky ringspot (CRS) is a widespread potato tuber necrotic disease caused by Tobacco rattle virus (TRV) infection. In the Pacific Northwest, this virus is transmitted by the stubby root nematode (SRN) within the genus Paratrichodorus. Remediating CRS affected fields is a major challenge that can be mitigated by growing plant varieties that are resistant to TRV infection. Growing alfalfa has been shown to reduce TRV levels in CRS infested fields over time but the development of a potato cultivar with these same capabilities would be of great economic benefit to potato growers. Castle Russet is a new potato clone that does not develop symptoms of CRS disease. To assess its ability to reduce soil virus load, Castle Russet, tobacco var. "Samsun NN", alfalfa var. "Vernema", and Russet Burbank potato were grown for a period of 1 to 3 months in soils containing viruliferous SRN populations at two different inoculation pressures (60 nematodes/pot and 1060 nematodes/pot) in greenhouse pot experiments. SRN population size and the presence of TRV were assessed over several months post inoculation. Results indicate that plant host and length of exposure significantly influence SRN population dynamics, whereas the TRV infection status of bait plants was significantly affected by both of these factors as well as inoculation pressure. These results suggest that both alfalfa var. "Vernema" and Castle Russet are resistant to TRV infection and may potentially be used to eliminate the virus from fields affected by CRS.

Transcriptome profiling of resistance response to Meloidogyne chitwoodi introgressed from wild species Solanum bulbocastanum into cultivated potato.

BACKGROUND: Meloidogyne chitwoodi commonly known as Columbia root-knot nematode or CRKN is one of the most devastating pests of potato in the Pacific Northwest of the United States of America. In addition to the roots, it infects potato tubers causing internal as well as external defects, thereby reducing the market value of the crop. Commercial potato varieties with CRKN resistance are currently unavailable. Race specific resistance to CRKN has been introgressed from the wild, diploid potato species Solanum bulbocastanum into the tetraploid advanced selection PA99N82-4 but there is limited knowledge about the nature of its resistance mechanism. In the present study, we performed histological and differential gene expression profiling to understand the mode of action of introgressed CRKN resistance in PA99N82-4 in comparison to the CRKN susceptible variety Russet Burbank. RESULTS: Histological studies revealed that the nematode juveniles successfully infect both resistant and susceptible root tissue by 48 h post inoculation, but the host resistance response restricts nematode feeding site formation in PA99N82-4. Differential gene expression analysis shows that 1268, 1261, 1102 and 2753 genes were up-regulated in PA99N82-4 at 48 h, 7 days, 14 days and 21 days post inoculation respectively, of which 61 genes were common across all the time points. These genes mapped to plant-pathogen interaction, plant hormonal signaling, antioxidant activity and cell wall re-enforcement pathways annotated for potato. CONCLUSION: The introgressed nematode resistance in PA99N82-4 is in the form of both pattern-triggered immune response and effector-triggered immune response, which is mediated by accumulation of reactive oxygen species and hypersensitive response (HR). Salicylic acid is playing a major role in the HR. Polyamines and suberin (a component of the Casperian strip in roots) also play an important role in mediating the resistance response. The present study provides the first ever comprehensive insights into transcriptional changes among M. chitwoodi resistant and susceptible potato genotypes after nematode inoculation. The knowledge generated in the present study has implications in breeding for CRKN resistance in potato.

Fluctuating survival selection explains variation in avian group size.

Most animal groups vary extensively in size. Because individuals in certain sizes of groups often have higher apparent fitness than those in other groups, why wide group size variation persists in most populations remains unexplained. We used a 30-y mark-recapture study of colonially breeding cliff swallows (Petrochelidon pyrrhonota) to show that the survival advantages of different colony sizes fluctuated among years. Colony size was under both stabilizing and directional selection in different years, and reversals in the sign of directional selection regularly occurred. Directional selection was predicted in part by drought conditions: birds in larger colonies tended to be favored in cooler and wetter years, and birds in smaller colonies in hotter and drier years. Oscillating selection on colony size likely reflected annual differences in food availability and the consequent importance of information transfer, and/or the level of ectoparasitism, with the net benefit of sociality varying under these different conditions. Averaged across years, there was no net directional change in selection on colony size. The wide range in cliff swallow group size is probably maintained by fluctuating survival selection and represents the first case, to our knowledge, in which fitness advantages of different group sizes regularly oscillate over time in a natural vertebrate population.

Parasites favour intermediate nestling mass and brood size in cliff swallows.

A challenge of life-history theory is to explain why animal body size does not continue to increase, given various advantages of larger size. In birds, body size of nestlings and the number of nestlings produced (brood size) have occasionally been shown to be constrained by higher predation on larger nestlings and those from larger broods. Parasites also are known to have strong effects on life-history traits in birds, but whether parasitism can be a driver for stabilizing selection on nestling body size or brood size is unknown. We studied patterns of first-year survival in cliff swallows (Petrochelidon pyrrhonota) in western Nebraska in relation to brood size and nestling body mass in nests under natural conditions and in those in which hematophagous ectoparasites had been removed by fumigation. Birds from parasitized nests showed highest first-year survival at the most common, intermediate brood-size and nestling-mass categories, but cliff swallows from nonparasitized nests had highest survival at the heaviest nestling masses and no relationship with brood size. A survival analysis suggested stabilizing selection on brood size and nestling mass in the presence (but not in the absence) of parasites. Parasites apparently favour intermediate offspring size and number in cliff swallows and produce the observed distributions of these traits, although the mechanisms are unclear. Our results emphasize the importance of parasites in life-history evolution.

Rapid induction of inflammatory lipid mediators by the inflammasome in vivo.

Detection of microbial products by host inflammasomes is an important mechanism of innate immune surveillance. Inflammasomes activate the caspase-1 (CASP1) protease, which processes the cytokines interleukin (IL)-1ß and IL-18, and initiates a lytic host cell death called pyroptosis. To identify novel CASP1 functions in vivo, we devised a strategy for cytosolic delivery of bacterial flagellin, a specific ligand for the NAIP5 (NLR family, apoptosis inhibitory protein 5)/NLRC4 (NLR family, CARD-domain-containing 4) inflammasome. Here we show that systemic inflammasome activation by flagellin leads to a loss of vascular fluid into the intestine and peritoneal cavity, resulting in rapid (less than 30 min) death in mice. This unexpected response depends on the inflammasome components NAIP5, NLRC4 and CASP1, but is independent of the production of IL-1ß or IL-18. Instead, inflammasome activation results, within minutes, in an 'eicosanoid storm'--a pathological release of signalling lipids, including prostaglandins and leukotrienes, that rapidly initiate inflammation and vascular fluid loss. Mice deficient in cyclooxygenase-1, a critical enzyme in prostaglandin biosynthesis, are resistant to these rapid pathological effects of systemic inflammasome activation by either flagellin or anthrax lethal toxin. Inflammasome-dependent biosynthesis of eicosanoids is mediated by the activation of cytosolic phospholipase A(2) in resident peritoneal macrophages, which are specifically primed for the production of eicosanoids by high expression of eicosanoid biosynthetic enzymes. Our results therefore identify eicosanoids as a previously unrecognized cell-type-specific signalling output of the inflammasome with marked physiological consequences in vivo.

Assessing Potato Cultivar Sensitivity to Tuber Necrosis Caused by Tobacco rattle virus.

Tobacco rattle virus (TRV) causes the economically important corky ring spot disease in potato. Chemical control is difficult due to the soilborne nature of the TRV-transmitting nematode vector, and identifying natural host resistance against TRV is considered to be the optimal control measure. The present study investigated the sensitivity of 63 cultivars representing all market types (evaluated at North Dakota and Washington over 2 years) for the incidence of TRV-induced tuber necrosis and severity. This article also investigates the cultivar-location interaction (using a mixed-effects model) for TRV-induced necrosis. TRV-induced tuber necrosis (P < 0.0001) and severity (P < 0.0001) were significantly different among cultivars evaluated separately in North Dakota and Washington trials. Mixed-effects model results of pooled data (North Dakota and Washington) demonstrated that the interaction of cultivar and location had a significant effect (P = 0.03) on TRV-induced necrosis. Based on the virus-induced tuber necrosis data from both years and locations, cultivars were categorized into sensitive, moderately sensitive, insensitive, and moderately insensitive groups. Based on data from North Dakota, 10 cultivars, including Bintje, Centennial Russet, Ciklamen, Gala, Lelah, Oneida Gold, POR06V12-3, Rio Colorado, Russian Banana, and Superior, were rated as insensitive to TRV-induced tuber necrosis. Similar trials assessing TRV sensitivity among cultivars conducted in Washington resulted in a number of differences in sensitivity rankings compared with North Dakota trials. A substantial shift in sensitivity of some potato cultivars to TRV-induced tuber necrosis was observed between the two locations. Four cultivars (Centennial Russet, Oneida Gold, Russian Banana, and Superior) ranked as insensitive for North Dakota trials were ranked as sensitive for Washington trials. These results can assist the potato industry in making cultivar choices to reduce the economic impact of TRV-induced tuber necrosis.