Abdel-Mohsen’s research focuses on understanding the role of host glycosylation machinery in viral persistence and immunopathogenesis.
Abdel-Mohsen joined The Wistar Institute as Assistant Professor in 2017 after completing his Ph.D. and postdoctoral training at the University of California, San Francisco (UCSF) and the Blood Systems Research Institute (BSRI), where he was subsequently appointed as a research scientist. Previously, he was a virologist for the World Health Organization Regional Reference Laboratory for poliovirus in his home country of Egypt. He received the UCSF-Gladstone CFAR Early-Career Award of Excellence in Basic Science in 2015.
The Abdel-Mohsen Laboratory
Illustration of the four areas in which the links between glycan-lectin interactions and immunology, and between immunology and HIV are described. Our laboratory is investigating the links between glycoimmunology and HIV persistence/immunopathogenesis within these areas.
Chronic inflammation has been associated with aberrant IgG glycosylation patterns and is prevalent in HIV+ individuals despite antiretroviral therapy (ART). Sialylated and galactosylated glycans have been associated with anti-inflammatory responses while bisected N-acetylglucosamine (GlcNAc) has been associated with pro-inflammatory responses. HIV infection causes pro-inflammatory changes, e.g., ART-irreversible loss of sialic acid and ART-reversible loss of galactose. Whether the HIV-induced changes in the circulating glycome are linked to chronic inflammation and HIV-associated co-morbidities (such as cardiovascular diseases and neurological impairments) is not clear. Asn = Asparagine.
Antibody-mediated effector functions are significantly affected by changes in IgG glycosylation and are important for preventing and controlling HIV infection. The presence of core fucose reduces antibody-dependent cellular cytotoxicity (ADCC), and the presence of galactose induces ADCC, antibody-dependent cellular phagocytosis (ADCP) and complement-dependent cytotoxicity (CDC). The size of the HIV reservoir, measured using nucleic acid-based methods (CD4+ T cell-associated HIV DNA and RNA), negatively associates with levels of non-fucosylated galactosylated glycans during suppressive ART. However, it is not clear if the documented roles of non-fucosylated galactosylated glycans in promoting ADCC and ADCP impact viral control during ART. C1q = Complement component 1q.
The potential role of the gut glycome in regulating the homeostatic relationship between the host and its gut microbiota during HIV infection. The potential role of the gut glycome in regulating the homeostatic relationship between the host and its gut microbiota, during HIV infection. The degree of glycosylation in the gut directly impacts the ability to maintain functional and healthy intestines. Here we give one example, by illustrating the role of gut fucosylation in the host-microbe interplay. Fucosylated glycans in the gut (left) enhance the beneficial activity of symbionts and improve resistance against colonization by pathogens and pathobionts. In the absence of gut fucosylation (right), beneficial symbionts are weakened and decreased in abundance, and pathogenic bacteria increase, which leads to microbial translocation, inflammation, and breakdown of the epithelial barrier. Fucosylated glycans are only one group out of many glycan structures composing the gut glycome. A change in the gut glycome may alter the distribution of microbial species. Therefore, it is possible that alterations in glycan metabolism may contribute to HIV-mediated intestinal damage, microbial translocation, and chronic inflammation.
Cell-surface glycan-lectin interactions mediate signals that define cellular processes and immunological functions, many of which are central to HIV infection. The specific structure of a glycan allows it to bind to specific glycan-binding proteins called lectins, leading to activation of downstream signaling pathways. These pathways are critical for a variety of cellular processes and immunological functions:
- T cells. Galectin-1 induces T cell apoptosis. Galectin-9 induces T-cell receptor (TCR) signaling, while galectin-3 reduces it. Galectin-3 alters T-cell function through interaction with LAG3 and other immune negative checkpoints. Last, the fucosylation of PD-1 impacts its function.
- NK cells. Siglecs-7 and -9 inhibit NK activity. Galectin-9 impairs NK function/cytotoxicity and cytokine production. Galectin-3 antagonizes NK cell-mediated antitumor immunity
- B cells. Siglec-6 induces B-cell exhaustion. Galectin-1 is a pre-B cell receptor ligand that induces receptor clustering, leading to efficient B cell differentiation. Galectin-9 suppresses B-cell receptor (BCR) signaling.
- T-regs. Galectins-1 and -9 can expand T-regs.
- Myeloid-derived suppressive cells (MDSC). The galectin-9/Tim3 interaction drives the expansion of CD11b+ly6G+ MDSC. Granulocytic MDSCs induce γδ-T cells to produce galectin-1, thus transforming them into immunosuppressive cells. These glycan-lectin interactions represent potential novel targets to enhance immune functionality during HIV infection to either cure HIV or prevent HIV-associated immune dysfunction and the subsequent development of immune dysfunction-associated diseases.
