scholarly journals Co-Therapy of Albendazole and Dexamethasone Reduces Pathological Changes in the Cerebral Parenchyma of Th-1 and Th-2 Dominant Mice Heavily Infected with Angiostrongylus cantonensis: Histopathological and RNA-seq Analyses

Biomolecules ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 536
Author(s):  
Kai-Yuan Jhan ◽  
Chien-Ju Cheng ◽  
Shih-Ming Jung ◽  
Yi-Jen Lai ◽  
Kuang-Yao Chen ◽  
...  

Administration of albendazole alone was not very suitable for the treatment of cerebral angiostrongyliasis. This study was designed to evaluate the effects of the co-therapy of this drug and dexamethasone in Th-1 and Th-2 dominant mice infected with Angiostrongylus cantonensis. Each of BALB/c and C57BL/6 mice infected with 50 A. cantonensis third-stage larvae were administered albendazole (10 mg/kg/day) alone, dexamethasone (0.5 mg/kg/day) alone, or co-therapy of the two drugs from day 7 or 14 post-infection for 7 or 14 days. After sacrifice, coronal slices were prepared from five brain regions and stained with hematoxylin and eosin. Eight pathological changes were employed to determine the therapeutic effectiveness using a scoring system. RNA-seq analysis was performed to confirm the histopathological findings. The infected BALB/c and C57BL/6 mice had similar patterns in the pathological changes. Meningitis, hemorrhage, size of worms, and encephalitis in the cerebral parenchyma were slighter in the mice treated with co-therapy than the remaining groups. Mice treated from day 14 had more severe changes than those from day 7. The histopathological findings were found to be consistent to immune responses determined by RNA-seq analysis. Co-therapy was determined to reduce pathological changes after administration to mice infected with A. cantonensis.

2018 ◽  
Vol 183 (4) ◽  
pp. 645-658 ◽  
Author(s):  
Jata Shankar ◽  
Gustavo C. Cerqueira ◽  
Jennifer R. Wortman ◽  
Karl V. Clemons ◽  
David A. Stevens

PLoS ONE ◽  
2013 ◽  
Vol 8 (8) ◽  
pp. e72084 ◽  
Author(s):  
Rong-Jyh Lin ◽  
Jie-Wen He ◽  
Li-Yu Chung ◽  
June-Der Lee ◽  
Jiun-Jye Wang ◽  
...  

2006 ◽  
Vol 13 (7) ◽  
pp. 733-739 ◽  
Author(s):  
Zhijun Wang ◽  
Li Xiang ◽  
Junjie Shao ◽  
Zhenghong Yuan

ABSTRACT In this article, the immunogenicity of tRNA and the recognition of tRNA by Toll-like receptors (TLRs) are analyzed. Analyses of the effects of different tRNAAla(UGC) fragments (tRNAAla1-76 [corresponding to positions 1 through 76], tRNAAla26-76, tRNAAla40-76, tRNAAla62-76, tRNAAla1-70, tRNAAla26-70, tRNAAla40-70, and tRNAAla62-70) on the immune responses of hepatitis B surface antigen (HBsAg) were performed with BALB/c mice. Results show that tRNAAla1-76, tRNAAla26-76, tRNAAla40-76, and tRNAAla62-76 adjuvants not only induced stronger T helper (Th) 1 immune responses but also cytotoxic-T-lymphocyte (CTL) responses relative to tRNAAla1-70, tRNAAla26-70, tRNAAla40-70, and tRNAAla62-70 adjuvants in HBsAg immunization. A deletion of the D loop (tRNAAla26-76), anticodon loop (tRNAAla40-76), or TψC (tRNAAla62-76) loop of tRNAAla(UGC) does not significantly decrease the adjuvant characteristic of tRNAAla(UGC). However a deletion of the 3′-end CCACCA sequence (tRNAAla1-70, tRNAAla26-70, tRNAAla40-70, and tRNAAla62-70) of tRNAAla(UGC) significantly decreased the adjuvant characteristic in Th1 and CTL immune responses. Moreover, the recognitions of different tRNAAla(UGC) fragments by TLR3, TLR7, TLR8, and TLR9 were analyzed. Results show that a deletion of the 3′ CCACCA sequence of tRNAAla(UGC) significantly decreased the recognition by TLR3. We concluded that the 3′ CCACCA sequence of tRNAAla(UGC) is the important motif to induce Th1 and CTL responses and this motif can be effectively recognized by TLR3.


2020 ◽  
Author(s):  
Daimon P. Simmons ◽  
Hung N. Nguyen ◽  
Emma Gomez-Rivas ◽  
Yunju Jeong ◽  
Antonia F. Chen ◽  
...  

AbstractMacrophages regulate protective immune responses to infectious microbes, but aberrant macrophage activation frequently drives pathological inflammation. To identify regulators of vigorous macrophage activation, we analyzed RNA-seq data from synovial macrophages and identified SLAMF7 as a receptor associated with a super-activated macrophage state in rheumatoid arthritis. We implicated IFN-γ as a key regulator of SLAMF7 expression. Engaging this receptor drove an exuberant wave of inflammatory cytokine expression, and induction of TNF-α following SLAMF7 engagement amplified inflammation through an autocrine signaling loop. We observed SLAMF7-induced gene programs not only in macrophages from rheumatoid arthritis patients, but in gut macrophages from active Crohn’s disease patients and lung macrophages from severe COVID-19 patients. This suggests a central role for SLAMF7 in macrophage super-activation with broad implications in pathology.


2015 ◽  
Vol 3 (1) ◽  
Author(s):  
Nathan D. Grubaugh ◽  
Aaron Massey ◽  
Katherine D. Shives ◽  
Mark D. Stenglein ◽  
Gregory D. Ebel ◽  
...  

Abstract Background.  West Nile virus (WNV) infection in humans can result in severe, acute encephalitis typically involving subcortical gray matter brain regions. West Nile virus replication within specific human brain regions from a human case of acute encephalitis has not been studied. Methods.  We describe a fatal case of WNV encephalitis in which we obtained tissue from specific brain regions at autopsy to evaluate viral-host interactions using next-generation sequencing and immunohistochemistry analysis. Results.  We found that WNV populations in the injured subcortical brain regions exhibited increased amino acid variation and increased expression of specific interferon genes compared with cortical tissues despite similar viral burden. Conclusions.  These observational, patient-based data suggest that neuronal injury and the strength of viral selection pressure may be associated with the level of the innate immune responses. Further studies in human and animal models evaluating the role of innate immune responses on injury patterns and viral selection pressure are needed.


2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
James P. Whitcomb ◽  
Mary DeAgostino ◽  
Mark Ballentine ◽  
Jun Fu ◽  
Martin Tenniswood ◽  
...  

Vitamin D signaling modulates a variety of immune responses. Here, we assessed the role of vitamin D in immunity to experimental leishmaniasis infection in vitamin D receptor-deficient mice (VDRKO). We observed that VDRKO mice on a genetically resistant background have decreasedLeishmania major-induced lesion development compared to wild-type (WT) mice; additionally, parasite loads in infected dermis were significantly lower at the height of infection. Enzymatic depletion of the active form of vitamin D mimics the ablation of VDR resulting in an increased resistance toL. major. Conversely, VDRKO or vitamin D-deficient mice on the susceptible Th2-biased background had no change in susceptibility. These studies indicate vitamin D deficiency, either through the ablation of VDR or elimination of its ligand, 1,25D3, leads to an increase resistance toL. majorinfection but only in a host that is predisposed for Th-1 immune responses.


1996 ◽  
Vol 184 (2) ◽  
pp. 771-775 ◽  
Author(s):  
B M Segal ◽  
E M Shevach

Inbred mice exhibit a spectrum of susceptibility to induction of experimental allergic encephalomyelitis (EAE). We have compared the immune responses of the susceptible SJL (H-2s) and resistant B10.S (H-2s) strains to determine factors other than the MHC background which control resistance/susceptibility to EAE. The resistance of the B10.S strain was found to be secondary to an antigen-specific defect in the generation of Th 1 cells that produce IFN gamma. This defect in IFN gamma production could be restored by exposure of the myelin basic protein (MBP)-reactive T cells to IL-12 with the subsequent induction of the ability to transfer EAE to naive recipients. These findings have important implications for the therapeutic use of IL-12 and IL-12 antagonists and may explain the association between relapses/exacerbation of autoimmune disease and infectious diseases.


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