Hyderabads’ CDFD researchers shed light on fungal pathogen’s immune evasion tactics
Tarnaka: Scientists of Hyderabad based Centre for DNA Fingerprinting and Diagnostics (CDFD) have discovered how Candida glabrata, a fungal pathogen, evades the human immune system.The research article titled ‘Aspartyl proteases target host actin nucleator complex protein to limit epithelial innate immunity’ was published in EMBO reports a prestigious journal.
Globally, more than 2.5 million people die from invasive fungal infections yearly. It naturally resides in the mouth, gut, and genitourinary tract of healthy individuals. “Candida glabrata causes fatal infections of the bloodstream and internal organs in patients with weakened immune systems. Candida glabrata, unlike other major fungal pathogens, does not form hyphal filaments that can penetrate into host tissues and aid in circumventing the immune system.
How does Candida glabrata hoodwink the host immune response?
The study, led by PhD student Sandip Patra under Dr. Rupinder Kaur, from Biotechnology Research and Innovation Council(BRIC), CDFD, focused on Candida glabrata’s interaction with epithelial cells. The researchers found that “Candida glabrata employs cell surface-associated aspartyl proteases to attack the epithelial cell protein Arpc1B, a subunit of the Arp2/3 complex that governs actin cytoskeleton branching,” said CDFD in an official statement.
Arpc1B is a subunit of the Arp2/3 complex that governs branching of the actin cytoskeleton. Candida glabrata-induced reduction in Arpc1B protein levels triggers a cascade of events that culminate in diminished secretion of the pro-inflammatory cytokine IL-8.
Since IL-8 attracts neutrophils, pathogen-killing innate immune cells, lower IL-8 secretion hampers their movement towards Candida glabrata, facilitating its survival in the host. CDFD in a statement, “This IL-8 plays a crucial role in attracting neutrophils, a type of immune cell that kills pathogens. With reduced IL-8 secretion, their movement towards Candida glabrata is hampered, allowing the fungus to survive within the host.”
This discovery is significant given that patients with Arpc1B gene mutations are prone to recurrent microbial infections.The findings open new possibilities for therapeutic interventions, potentially involving Arp2/3 complex augmentation to combat infectious diseases.
How do the findings help?
The research contributes to our understanding of fungal disease progression, a critical area of study considering invasive fungal infections. Funded by the DBT/Wellcome Trust India Alliance, this study findings, newly published in the journal EMBO Reports, pave a path forward for the researchers to explore a novel therapeutic avenue involving Arp2/3 complex augmentation, for infectious diseases. It offers promising avenues for developing targeted treatments against fungal infections, particularly in immunocompromised individuals.