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Effects of Experimental Sarcocystis neurona-Induced Infection on Immunity in an Equine Model.

Lewis SR, Ellison SP, Dascanio JJ, Lindsay DS, Gogal RM, Werre SR, Surendran N, Breen ME, Heid BM, Andrews FM, Buechner-Maxwell VA, Witonsky SG - J Vet Med (2014)

Bottom Line: Neurologic parameters were recorded prior to and throughout the 70-day study by blinded investigators.Recombinant SnSAG1 ELISA for serum and CSF were used to confirm and track disease progression.Neutrophils, monocytes, and lymphocytes from infected horses displayed significantly delayed apoptosis at some time points.

View Article: PubMed Central - PubMed

Affiliation: Department of Large Animal Clinical Sciences, Virginia-Maryland Regional College of Veterinary Medicine, Blacksburg, VA 24061, USA ; Rangiora Veterinary Centre, Rangiora 7400, New Zealand.

ABSTRACT
Sarcocystis neurona is the most common cause of Equine Protozoal Myeloencephalitis (EPM), affecting 0.5-1% horses in the United States during their lifetimes. The objective of this study was to evaluate the equine immune responses in an experimentally induced Sarcocystis neurona infection model. Neurologic parameters were recorded prior to and throughout the 70-day study by blinded investigators. Recombinant SnSAG1 ELISA for serum and CSF were used to confirm and track disease progression. All experimentally infected horses displayed neurologic signs after infection. Neutrophils, monocytes, and lymphocytes from infected horses displayed significantly delayed apoptosis at some time points. Cell proliferation was significantly increased in S. neurona-infected horses when stimulated nonspecifically with PMA/I but significantly decreased when stimulated with S. neurona compared to controls. Collectively, our results suggest that horses experimentally infected with S. neurona manifest impaired antigen specific response to S. neurona, which could be a function of altered antigen presentation, lack of antigen recognition, or both.

No MeSH data available.


Related in: MedlinePlus

Neurologic scores by (a) individual total non-experimentally infected neurologic score control (top) and (b) S. neurona experimentally infected (bottom) horses. All horses were scored biweekly via a comprehensive neurologic panel. Each parameter was assessed a score from 0 (normal) to 3 (very abnormal), with a maximum of 97. (a) Total neurologic score is reported. Baseline = preacclimatization score. Week −1 = score following acclimatization, but prior to infection. Week 1 = first week of infection with S. neurona. Results are reported by baseline-individual horse response by day and the average response of the horses by treatment by day.
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fig2: Neurologic scores by (a) individual total non-experimentally infected neurologic score control (top) and (b) S. neurona experimentally infected (bottom) horses. All horses were scored biweekly via a comprehensive neurologic panel. Each parameter was assessed a score from 0 (normal) to 3 (very abnormal), with a maximum of 97. (a) Total neurologic score is reported. Baseline = preacclimatization score. Week −1 = score following acclimatization, but prior to infection. Week 1 = first week of infection with S. neurona. Results are reported by baseline-individual horse response by day and the average response of the horses by treatment by day.

Mentions: While all 5 S. neurona-inoculated horses exhibited neurologic signs and had an increased neurologic score over the course of the study, horses varied as to when their neurologic deficits were most significant (Figure 2). Initial neurologic signs were noted on day 5 of infection and on day 10 after infection. All S. neurona challenged horses displayed progressive clinical disease with moderate to severe neurologic signs (Figure 3). The neurologic signs included, but were not limited to, cranial nerve deficits, changes in attitude, and ataxia. The level of neurologic deficits was higher than anticipated, and as a result, the decision to stop the infection process on day 10 was made based on genuine concern for the health of the horses. According to Ellison (via phone communication), horses already displaying this level of neurologic deficits would become progressively worse from this time point, and it was therefore anticipated that these horses would progress to a Grade II status by day 60 after infection (the standard level of ataxia induced with this dose and model) [18–20]. Neurologic scores for horse 3 peaked within the first 14 days after infection, and horses 5, 6, 7, and 9 peaked between days 42–56 of the experiment. All experimentally S. neurona-infected, except horse 7, and non-experimentally infected control horses, except horse 8, had a higher score on day 56. All S. neurona-infected horses demonstrated a detectable level of ataxia compared to control horses at days 7, 21, and 70 (data not shown) Experimentally infected horses exhibited a peak in cranial nerve signs prior to the peak in ataxia, the latter of which was more pronounced towards the end of the study period. Logarithmic values were used in the statistical analysis in an attempt to stabilize the variance and as these were closer to a straight line on the normal probability plots. A significant difference (P < 0.05) between the control and infected population's mean overall neurologic score was present on day 70. A trend towards a difference (0.05 < P < 0.1) was seen at days 7 and 28.


Effects of Experimental Sarcocystis neurona-Induced Infection on Immunity in an Equine Model.

Lewis SR, Ellison SP, Dascanio JJ, Lindsay DS, Gogal RM, Werre SR, Surendran N, Breen ME, Heid BM, Andrews FM, Buechner-Maxwell VA, Witonsky SG - J Vet Med (2014)

Neurologic scores by (a) individual total non-experimentally infected neurologic score control (top) and (b) S. neurona experimentally infected (bottom) horses. All horses were scored biweekly via a comprehensive neurologic panel. Each parameter was assessed a score from 0 (normal) to 3 (very abnormal), with a maximum of 97. (a) Total neurologic score is reported. Baseline = preacclimatization score. Week −1 = score following acclimatization, but prior to infection. Week 1 = first week of infection with S. neurona. Results are reported by baseline-individual horse response by day and the average response of the horses by treatment by day.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4590861&req=5

fig2: Neurologic scores by (a) individual total non-experimentally infected neurologic score control (top) and (b) S. neurona experimentally infected (bottom) horses. All horses were scored biweekly via a comprehensive neurologic panel. Each parameter was assessed a score from 0 (normal) to 3 (very abnormal), with a maximum of 97. (a) Total neurologic score is reported. Baseline = preacclimatization score. Week −1 = score following acclimatization, but prior to infection. Week 1 = first week of infection with S. neurona. Results are reported by baseline-individual horse response by day and the average response of the horses by treatment by day.
Mentions: While all 5 S. neurona-inoculated horses exhibited neurologic signs and had an increased neurologic score over the course of the study, horses varied as to when their neurologic deficits were most significant (Figure 2). Initial neurologic signs were noted on day 5 of infection and on day 10 after infection. All S. neurona challenged horses displayed progressive clinical disease with moderate to severe neurologic signs (Figure 3). The neurologic signs included, but were not limited to, cranial nerve deficits, changes in attitude, and ataxia. The level of neurologic deficits was higher than anticipated, and as a result, the decision to stop the infection process on day 10 was made based on genuine concern for the health of the horses. According to Ellison (via phone communication), horses already displaying this level of neurologic deficits would become progressively worse from this time point, and it was therefore anticipated that these horses would progress to a Grade II status by day 60 after infection (the standard level of ataxia induced with this dose and model) [18–20]. Neurologic scores for horse 3 peaked within the first 14 days after infection, and horses 5, 6, 7, and 9 peaked between days 42–56 of the experiment. All experimentally S. neurona-infected, except horse 7, and non-experimentally infected control horses, except horse 8, had a higher score on day 56. All S. neurona-infected horses demonstrated a detectable level of ataxia compared to control horses at days 7, 21, and 70 (data not shown) Experimentally infected horses exhibited a peak in cranial nerve signs prior to the peak in ataxia, the latter of which was more pronounced towards the end of the study period. Logarithmic values were used in the statistical analysis in an attempt to stabilize the variance and as these were closer to a straight line on the normal probability plots. A significant difference (P < 0.05) between the control and infected population's mean overall neurologic score was present on day 70. A trend towards a difference (0.05 < P < 0.1) was seen at days 7 and 28.

Bottom Line: Neurologic parameters were recorded prior to and throughout the 70-day study by blinded investigators.Recombinant SnSAG1 ELISA for serum and CSF were used to confirm and track disease progression.Neutrophils, monocytes, and lymphocytes from infected horses displayed significantly delayed apoptosis at some time points.

View Article: PubMed Central - PubMed

Affiliation: Department of Large Animal Clinical Sciences, Virginia-Maryland Regional College of Veterinary Medicine, Blacksburg, VA 24061, USA ; Rangiora Veterinary Centre, Rangiora 7400, New Zealand.

ABSTRACT
Sarcocystis neurona is the most common cause of Equine Protozoal Myeloencephalitis (EPM), affecting 0.5-1% horses in the United States during their lifetimes. The objective of this study was to evaluate the equine immune responses in an experimentally induced Sarcocystis neurona infection model. Neurologic parameters were recorded prior to and throughout the 70-day study by blinded investigators. Recombinant SnSAG1 ELISA for serum and CSF were used to confirm and track disease progression. All experimentally infected horses displayed neurologic signs after infection. Neutrophils, monocytes, and lymphocytes from infected horses displayed significantly delayed apoptosis at some time points. Cell proliferation was significantly increased in S. neurona-infected horses when stimulated nonspecifically with PMA/I but significantly decreased when stimulated with S. neurona compared to controls. Collectively, our results suggest that horses experimentally infected with S. neurona manifest impaired antigen specific response to S. neurona, which could be a function of altered antigen presentation, lack of antigen recognition, or both.

No MeSH data available.


Related in: MedlinePlus