Numerous studies identify that IP-10 and IFN-γ are involved in leucocyte migration and activation and regarded as promising surrogate biomarkers in human and bovine tuberculosis infection, but there is lack of evidence for IP-10 in nonhuman primates. In this study, we directly determined IP-10 and IFN-γ levels in plasma from 30 healthy monkeys, 30 monkeys with naturally acquired tuberculosis, 4 monkeys experimentally infected with tuberculosis, and PPD stimulated whole blood of 14 monkeys with naturally acquired tuberculosis by ELISA. Higher plasma levels of IP-10 and IFN-γ were observed in natural tuberculosis monkeys than in healthy controls. The dynamic changes of plasma IP-10 and IFN-γ in experimental infections showed consistent representation of a transient increase during the infection period. After PPD stimulation, release of IP-10 and IFN-γ is significantly induced in natural tuberculosis monkeys, but the stimulation index of IP-10 was significantly lower than IFN-γ. Further analysis showed that positive correlation between IP-10 and IFN-γ existed in healthy and tuberculosis monkeys. Our findings support plasma IP-10 and IFN-γ as biomarkers for monitoring ongoing inflammation of nonhuman primate tuberculosis, and IFN-γ is a more valuable diagnostic biomarker.
Background
Currently, Chinese laboratory macaques are widely used in biomedical research. Correspondingly, clarity regarding the genetic diversity of Chinese laboratory macaques is important for both vendors and users.
Methods
Genome sequences of 55 laboratory macaques (40 cynomolgus macaques and 15 rhesus macaques) bred in South China were analyzed using 2b‐RAD simplified genome sequencing.
Results
A total of 115,681 single‐nucleotide polymorphisms (SNPs) were found that were distributed in 21 chromosomes and an unplaced scaffold. Genetic diversity indices varied across populations and exhibited low values. The results of principal coordinate analysis (PCA) were consistent with those of the arithmetic mean (UPGMA) clustered tree and supported the structure analysis, demonstrating that the genetic differentiation in rhesus macaques was higher than that in cynomolgus macaques. Introgressive hybridization with the Chinese rhesus macaque was supported in more than 80% (32/40) of cynomolgus macaques.
Conclusions
Chinese laboratory macaques had relatively low genetic diversity at the genomic level, and genetic differentiation in Chinese rhesus macaques was higher than in cynomolgus macaques. The genome of cynomolgus macaques has been shaped by introgression after hybridization with the Chinese rhesus macaques.
We report on the first detection and isolation of B. pseudohinzii (Bordetella pseudohinzii) in laboratory mice in China. Forty‐one B. pseudohinzii strains were isolated from 3094 mice in 33 different laboratory animal facilities in southern China. The isolates were identified through culture and genome sequenceing. Phylogenetic analysis based on the sequences of 16S rRNA and OmpA genes demonstrated that these strains were on the same clade as other B. pseudohinzii strains isolated from mice. Experimental infected mice presented an asymptomatic infection. B. pseudohinzii replicated in both the respiratory tract and the digestive tract. Most importantly B. pseudohinzii shed via feces and infected a group of sentinel mice in a separate cage via cage padding contaminated with B. pseudohinzii‐positive feces, indicating that B. pseudohinzii could transmit efficiently among mice and contaminate environmental facilities. Our study highlights the importance of routine monitoring of the pathogen in laboratory mice and provides vital insights into the transmission of Brodetellae in rodents and human.
To profile the dynamic changes of immune responses for M. kansasii infection, 3 cynomolgus monkeys were experimentally infected with M. kansasii by intratracheal inhalation of 1 × 106 CFU bacteria per monkey. Every 2 to 4 weeks, tuberculin skin testings (TSTs) were performed and blood samples were collected for immunoassay. Multiple cytokines in a single sample were measured by Luminex xMAP technologies. IgM and IgA were detected by double-antibody sandwich ELISA. IgG against PPD and 11 M. tuberculosis proteins were detected by using of indirect ELISA. At week 16, all animals were euthanized for necropsy and histological analysis. Positivities of TSTs emerged from week 2 to 6 postinfection. Leukocyte counts and T lymphocyte subsets experienced moderate increases. Among 44 kinds of cytokines, 36 kinds of them showed increases of different dynamic types and 8 kinds of them showed no specific changes. Total IgM and IgA showed a transient increase at an early infection stage. Positivities of M. tuberculosis specific IgM and IgA emerged as early as week 2 postinfection. All animals showed positive IgG against PPD and negative IgG responses to 38 kDa, MPT64L, TB16.3, 16 kDa, U1, and MTB81 antigens during the infection period. IgG against ESAT-6, CFP10, CFP10-ESAT-6, Ag85b, and 14 kDa antigens reached positive levels. The IgG avidities of PPD, ESAT-6, CFP10-ESAT-6, and Ag85b were all above 50 percent. In conclusion, the data indicate that M. kansasii infection in monkeys can induce positivities of TSTs, increases of multiple cytokines, and cross-reactive antibody responses to M. tuberculosis antigens.
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