Receptor for Advanced Glycation End Product (RAGE) Modulates Inflammation During Feeding of the Hard Tick, Haemaphysalis longicornis in Mice.

Ticks are notorious blood-sucking ectoparasites that affect both humans and animals. They serve as a unique vector of various deadly diseases. Here, we have shown the roles of the receptor for advanced glycation end products (RAGE) during repeated infestations by the tick Haemaphysalis longicornis using RAGE-/- mice. In primary infestation, a large blood pool developed, which was flooded with numerous RBCs, especially during the rapid feeding phase of the tick both in wild-type (wt) and RAGE-/- mice. Very few inflammatory cells were detected around the zones of haemorrhage in the primary infestations. However, the number of inflammatory cells gradually increased in the subsequent tick infestations, and during the third infestations, the number of inflammatory cells reached to the highest level (350.3 ± 16.8 cells/focus). The site of attachment was totally occupied by the inflammatory cells in wt mice, whereas very few cells were detected at the ticks' biting sites in RAGE-/- mice. RAGE was highly expressed during the third infestation in wt mice. In the third infestation, infiltration of CD44+ lymphocytes, eosinophils and expression of S100A8 and S100B significantly increased at the biting sites of ticks in wt, but not in RAGE-/- mice. In addition, peripheral eosinophil counts significantly increased in wt but not in RAGE-/- mice. Taken together, our study revealed that RAGE-mediated inflammation and eosinophils played crucial roles in the tick-induced inflammatory reactions.

Zoonotic human liver flukes, a type 1 biocarcinogen, in freshwater fishes: genetic analysis and confirmation of molluscan vectors and reservoir hosts in Bangladesh.

BACKGROUND: Opisthorchiid flukes, particularly Opisthorchis viverrini, Opisthorchis felineus, Clonorchis sinensis, and Metorchis spp. are the most common fish-borne zoonotic human liver flukes (hLFs). Liver fluke infections are more prevalent in resource-deprived and underprivileged areas. We herein estimated the prevalence of the metacercariae (MC) of major hLFs in common large freshwater fishes (lFWF) marketed for human consumption from some selected areas of Bangladesh along with detection of their molluscan vectors and reservoirs. METHODS: The current status of fish-borne zoonotic hLF infections in lFWF was investigated along with their molluscan vectors and mammalian reservoir hosts in Mymensingh and Kishoreganj in Bangladesh from July 2018-June 2022 using conventional and multiple molecular techniques, such as PCR, PCR-restriction fragment length polymorphism (RFLP), sequencing, and bioinformatic analyses. The infection rate of fishes was analyzed using the Z-test and the loads of MC were compared using the chi-squared (χ2) test. RESULTS: The MC of C. sinensis, Opisthorchis spp., and Metorchis spp. were detected in 11 species of common and popular lFWF. In lFWF, the estimated prevalence was 18.7% and the mean load was 137.4 ± 149.8 MC per 100 g of fish. The prevalence was the highest (P < 0.05) in spotted snakehead fishes (Channa punctata, 63.6%). The highest rate of infection (P < 0.05) was observed with the MC of C. sinensis (11.8%). Metacercariae were almost equally (P > 0.05) distributed between the head and body of fishes. The infection rate was slightly higher in cultured (19.6%) fishes. The MC of C. sinensis, O. felineus, O. viverrini, and Metorchis orientalis in fishes were confirmed using PCR, PCR-RFLP and bioinformatics. The cercariae of opisthorchiid (Pleurolophocercus cercariae) flukes were only recovered from Bithynia spp. (3.9%, 42 out of 1089). The ova of hLFs from dogs (4.3%, 5 out of 116) and cats (6.0%, 6 out of 100), and adult flukes (M. orientalis) from ducks (41.1% 113 out of 275) were detected. CONCLUSIONS: The MC of hLFs are highly prevalent in fresh water fishes in Bangladesh. Reservoir hosts, such as street dogs, cats, and ducks carried the patent infection, and residents of Bangladesh are at risk.