Every day, countless new infections occur worldwide, and a large percentage of sexually active individuals may get STIs by the age of 25. Viruses (HIV) often enter the body through the skin and mucous membranes. The best defense against these infections is vaccination. But to design effective vaccines, it is crucial to understand the immune cells in these tissues and how they interact with these viruses. Recent studies have revealed the complex role of these cells, which may lead to significant advances in vaccine development.
Researchers at the University of Sydney Medical Research Institute, led by Professor Andrew Harman, have made great progress in understanding immune cells that reside in the squamous epithelium (SSE) stratified by the skin and mucosal membranes. Including Erica Vine Kirstie Bertram, Associate Professor Paul Austin, Dr. Thomas O’Neil, Dr. Najla Nasr and Professor Anthony Cunningham published their findings in the journal, providing new insights that could revolutionize mucosal vaccine design.
SSE forms the outermost layer of the skin and certain mucosal tissues, which is a key obstacle to targeting pathogens. Historically, Langerhans cells (LCS) have been considered to be the only antigen presenting cell (APC) within SSE. However, recent studies identified another key player: dendritic cells (DCs). These findings have profound implications for the development of next-generation vaccines targeting the skin and mucous membrane surfaces.
“Our study highlights the different roles of LCS cells and DCs in pathogen uptake and immune activation. This distinction is crucial for designing vaccines that can effectively utilize the unique functions of these cells.” The study highlights the correctness The importance of identifying and characterizing these APCs to enhance vaccine efficacy.
One of the key revelations of this study is the functional differences between LCS and DC. Although both cell types are involved in the detection and processing of pathogens, they exhibit different mechanisms of pathogen uptake and T cell activation. It is worth noting that DCs have been shown to be more effective in certain immune responses, although their role in neuroimmune interactions remains to be fully understood.
The implications of these findings are particularly relevant to mucosal vaccines, which aim to induce immunity at sites of pathogen entry, such as the genital and respiratory tract. Given that sexually transmitted infections (sexually transmitted infections) and other viral infections such as MPOX, herpes simplex virus (HSV) and human immunodeficiency virus (HIV) often enter the body through these routes, thus optimizing vaccine delivery to these areas, this is to Crucial.
The research team also highlights the historical development of our understanding of APC in SSE. Initially, LC was the main focus, but identification of epithelial DCs has expanded the landscape of immune defense mechanisms in these tissues. This evolution emphasizes the dynamic nature of immunological research and the ongoing need to update our knowledge base through new discoveries.
Professor Harman pointed out: “The identification of DCs in SSE opens up new avenues for vaccine development. By leveraging the unique properties of these cells, we can design more targeted and effective vaccines that can provide strong protection for a variety of pathogens. “This approach may be particularly beneficial in creating vaccines that cause strong local immune responses at the site of infection.
Furthermore, this study elucidates neuroimmune interactions within SSE. The presence of nerve ends that interact with immune cells suggests a complex interaction that affects the immune response. “We are at the beginning of unveiling these two-way interactions, which represent new and untapped boundaries in vaccine science,” said Associate Professor Austin. Understanding these interactions can inform the development of vaccines and therapies that regulate immune activity through neural pathways.
In summary, the research conducted by Professor Harman and colleagues marks a significant advance in our understanding of the immune landscape in SSE. By describing the role of LCS and DCS, this study provides the basis for the development of more effective mucosal vaccines. As communities around the world continue to fight infectious diseases, such innovation is crucial to improving public health outcomes.
Journal Reference
Vine, EE, Austin, PJ, O’Neil, TR, NASR, N., Bertram, KM, Km, Cunningham, Al, & Harman, An (2024). Epithelial dendritic cells and Langerhans cells: Effects on mucosal vaccines. Cell Reports, 43. doi: https://doi.org/10.1016/j.celrep.2024.113977
Other references
Bertram KM, Botting RA, Baharlou B, Rhodes JW, Rana H, Graham JD, Patrick E, Fletcher J, Plasto TM, Truong NR, Royle C, Doyle CM, Tong O, Nasr N, Nasr N, Barnouti L, Bar nouti L , Kohout MP, Brooks AJ, Brooks AJ, Brooks AJ, Brooks AJ, Wines MP, Haertsch P, Lim J, Gosselink MP, Ctercteko G, Estes JD, Churchill MJ, Cameron PU, Hunter E Hani ffa MA, Cunningham AL, Haman Identification of HIV-transmitted CD11C+ human epidermal dendritic cells Natural Communications 2019 PMID: 31227717.
Bertram KM, Truong NR, Smith JB, Kim M, Sandgren KJ, Feng KL, Herbert J, Rana H, Danastas K, Miranda M, Rhodes JW, Patrick E, Cohen RC, Lim J, Merten S, Merten S : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : : , Harman* Al*. Herpes simplex virus type 1 infects Langerhan cells and novel epidermal dendritic cells Epi-cdc2s through different entrance pathways PLOS pathogen 2021. PMID: 33905459. *Equal to the previous author
Bertram KM, O’Neil TR, Vine EE, Baharlou H, Cunningham AL, Harman An. Defines the landscape of human epidermal mononuclear phagocytocytes. Immune 2023. PMID: 36921567.
About the Author
Andrew Harman He studied his PhD at Cambridge University, studying how herpes simplex virus enters cells and establishes epidermal infections. He moved to the Westmead Health area in 2002 and is now a professor of virus and immunology at the University of Sydney’s School of Medical Sciences and co-director of the Centre for Virus Research at the Westmead Medical Institute. He has established partnerships with more than 30 clinicians, giving him unique access to a wide range of human tissue he has freshly discarded from surgery, affected by a range of disease conditions. He has two NHMRC ideas as a grant from the Central Intelligence Agency (CIA), which have funded research groups that study the sexual transmission of HIV and inflammatory bowel disease. Importantly, he has identified a new population of dendritic cells that inhabit the stratified squamous epithelium, in addition to Langerhans’ cells.
