Abstract—Lysosomal cysteine proteases play important roles in our immune-system by processing pathogens but their involvement in fungal mediated diseases remains unknown. In this study with the help of using various techniques such as immunoblotting, enzyme activity profile and ELISA, we observed that cysteine proteases (cathepsin B, L and C) are involved in fungal disease progression. In the mice model of pulmonary aspergillosis, cathepsin (CP)B and CPL activities were observed significantly high while the activity level for CPC was found low. Conversely, treatment of these infected mice with antifungal compounds showed statistically decreases in the activity of CPB (p<0.05) without significant change in CPL and CPC activities, demonstrating CPB role in fungal infection. Notably, altered in the cytokines levels i.e., decreased in IL-4 and increased in IFN- in antifungal treated mice further support the resistant effect of antifungal compounds to fungal infection. Importantly, this alteration in cytokines levels is similar to CPB activity profile additionally depicts the regulatory effect of this protease in fungal infection. The involvement of lysosome in this process was confirmed by a lysosomal marker i.e., acid phosphatase. Present study reveals a novel interaction between cysteine protease and pulmonary aspergillosis and illustrates a possible negative role of CPB in fungal infection, due to that it could act as an important therapeutic target and early biomarker for this disease.

Index Terms—A. fumigatus, Cathepsins, Antifungal compounds.

Ashwani Mittal, Biochemistry Department, Kurukshetra University, Kurukshetra, Haryana – 136119 (e-mail: amittal@kuk.ac.in)
TK Mandal, Regional Research Institute (Ay), (Central Council for Research in Ayurveda and Siddha), Nehru Garden, Kothrud, Pune – 411 038 (e-mail: drmandaltk@yahoo.com)
Rajat Bindal, Biotechnology Department, Seth Jai Parkash Mukund Lal, Institute of Engg. & Technology, Radaur, Kurukshetra University, Kurukshetra, Haryana – 136119 (e-mail: rajat.rickey@gmail.com)
Rajesh Dabur, Regional Research Institute (Ay), (Central Council for Research in Ayurveda and Siddha), Nehru Garden, Kothrud, Pune – 411 038 (Tel No: + (912025383138); fax: +(912025386715). e-mail: rajeshdabur@yahoo.com.

Cite: Ashwani Mittal, TK Mandal, Rajat Bindal, and Rajesh Dabur, "Cathepsin B is a Negative Regulator in Pulmonary Aspergillosis," International Journal of Bioscience, Biochemistry and Bioinformatics vol. 1, no. 2, pp. 125-130, 2011.