Harnessing Immune Evasion Strategy of Lymphatic Filariae: A Therapeutic Approach against Inflammatory and Infective Pathology

Abstract

Human lymphatic filariae have evolved numerous immune evasion strategies to secure their long-term survival in a host. These strategies include regulation of pattern recognition receptors, mimicry with host glycans and immune molecules, manipulation of innate and adaptive immune cells, induction of apoptosis in effector immune cells, and neutralization of free radicals. This creates an anti-inflammatory and immunoregulatory milieu in the host: a modified Th2 immune response. Therefore, targeting filarial immunomodulators and manipulating the filariae-driven immune system against the filariae can be a potential therapeutic and prophylactic strategy. Filariae-derived immunosuppression can also be exploited to treat other inflammatory diseases and immunopathologic states of parasitic diseases, such as cerebral malaria, and to prevent leishmaniasis. This paper reviews immunomodulatory mechanisms acquired by these filariae for their own survival and their potential application in the development of novel therapeutic approaches against parasitic and inflammatory diseases. Insight into the intricate network of host immune-parasite interactions would aid in the development of effective immune-therapeutic options for both infectious and immune-pathological diseases.

microRNAs: Critical Players during Helminth Infections

“…Filarial parasites employ several strategies to evade the immune response during infection. Most of these strategies are orchestrated by ES, which interferes with the functions of the host’s intracellular and extracellular immune machinery [ 127 ]. Thus, parasite miRNAs have relevant roles in parasite biology and immune dysfunction in the host [ 128 , 129 ].…”

Defining the filarial N-glycoproteome by glycosite mapping in the human parasitic nematode Brugia malayi

“…Parasite mediated interactions with the mammalian host such as immunomodulation and immune evasion allow B. malayi and other larial parasites to exist for many years in immunocompetent hosts and represent an active area of investigation 7 . Glycoconjugates present at the worm surface, secreted, excreted, or present in extracellular vesicles released by the parasite into the host are all part of crucial mechanisms that allow these parasites to exist for years without clearance [8][9][10][11] . Detailed characterization of these critical molecules and their synthesis pathways can highlight candidate biomarkers, therapeutic targets, vaccine molecules or diagnostic tools for further development.…”

Defining the filarial N-glycoproteome by glycosite mapping in the human parasitic nematode Brugia malayi

“…Parasite mediated interactions with the mammalian host such as immunomodulation and immune evasion allow B. malayi and other filarial parasites to exist for many years in immunocompetent hosts and represent an active area of investigation 7 . Glycoconjugates present at the worm surface, secreted, excreted, or present in extracellular vesicles released by the parasite into the host are all part of crucial mechanisms that allow these parasites to exist for years without clearance 8 – 11 . Detailed characterization of these critical molecules and their synthesis pathways can highlight candidate biomarkers, therapeutic targets, vaccine molecules or diagnostic tools for further development.…”