Effects Of Complement Opsonization Of Hiv On Dendritic Cells

Dendritic cells are key players during HIV pathogenesis, and shape both the immediate immune response at the site of infection as well as directing the adaptive immune response against the virus. HIV has developed a plethora of immune evasion mechanisms that hijack dendritic cell functions, suppressing their ability to mount an accurate immune response and exploiting them for efficient viral transfer to target T cells. To achieve successful replication within dendritic cells without triggering danger signaling, HIV accomplishes a delicate balance where only a low level of transcription can be sustained without triggering antiviral responses that would harm the virus. Here, we describe how the presence of HSV2 coinfection, which is very common in geographic areas with a high HIV prevalence and almost triples the risk of HIV acquisition, alters dendritic cell state to support much higher levels of HIV infection. We found this effect to be mediated by the STING pathway, which is involved in the sensing of DNA in the cell cytosol. STING activation led to an upregulation of factors such as IRF3 and NFkB that can be used for HIV transcription and a degradation of factors that restrict HIV replication. In addition, we describe how HIV exploits the human complement system, a group of proteins that usually help the human body to identify dangerous pathogens while avoiding reaction towards self. HIV can coat itself, i.e. become opsonized, in complement fragments that are typically only present on the body’s own cells, allowing it to activate signaling pathways that are associated with tolerance. Dendritic cells that come into contact with complement opsonized HIV do not mount danger responses, despite the fact that HIV-derived single stranded RNA triggers the pathogen recognition receptor TLR8. The suppression of danger responses is mediated by activation of complement receptor 3, and leads to an increased infection of the dendritic cell and affects its interactions with other immune cells. There is a lack of recruitment of NK cells to the site of infection, and an inhibition of NK cell killing, which plays an important role in the destruction of HIV-infected cells in vivo. T cells primed by dendritic cells exposed to complement opsonized HIV have a lower ability to develop towards effector phenotype, and have an increased expression of the markers PD1, TIM3 and LAG3 which are associated with T cell dysfunction and exhaustion. In addition, T cells primed by these dendritic cells in the presence of NK cells upregulate markers CD38, CXCR3 and CCR4, which have been linked to an increased susceptibility to HIV infection. In summary, we add to the current knowledge on HIV immune evasion mechanisms that allow the virus to establish infection, as well as describing mechanisms that govern whether dendritic cells mount danger signaling and an immune response or not.

This book gives a comprehensive overview of HIV and AIDS including NeuroAIDS, as well as general concepts of pathology, immunity and immunopathology, diagnosis, treatment, epidemiology and etiology to current clinical recommendations in management of HIV/AIDS including NeuroAIDS, highlighting the ongoing issues, recent advances and future directions in diagnostic approaches and therapeutic strategies.

Currently, more than 36 million people are infected with HIV. Although the introduction of highly active anti-retroviral therapy (HAART) has led to substantial advances in the clinical management of HIV infected individuals, HAART cannot completely eliminate the virus. This is because CD4 T helper cells, harboring the virus, remain dormant reservoirs. These reservoirs are difficult to measure and are present even in HAART-treated HIV infected individuals with undetectable levels of HIV in the blood. A growing body of studies has revealed follicular helper (Tfh) CD4 T cells, a highly differentiated CD4 T cell population localized in immunologically sanctuary sites (follicle/germinal center), as a major reservoir of HIV. The present Frontiers in Immunology eBook compiles 16 timely review articles focusing on the dynamics of major follicular immune cell types in HIV/SIV infection and their potential role for disease pathogenesis and the viral persistence in the lymph node. This eBook provides a comprehensive presentation of recent published work on lymph node and especially Tfh cell dynamics in HIV infection and we hope that it will be useful for our further understanding of how such dynamics affect the interplay between virus and host as well as for the discovery of novel therapeutic targets in the fight against HIV.

The Janeway's Immunobiology CD-ROM, Immunobiology Interactive, is included with each book, and can be purchased separately. It contains animations and videos with voiceover narration, as well as the figures from the text for presentation purposes.

Antibody Fc is the first single text to synthesize the literature on the mechanisms underlying the dramatic variability of antibodies to influence the immune response. The book demonstrates the importance of the Fc domain, including protective mechanisms, effector cell types, genetic data, and variability in Fc domain function. This volume is a critical single-source reference for researchers in vaccine discovery, immunologists, microbiologists, oncologists and protein engineers as well as graduate students in immunology and vaccinology. Antibodies represent the correlate of protection for numerous vaccines and are the most rapidly growing class of drugs, with applications ranging from cancer and infectious disease to autoimmunity. Researchers have long understood the variable domain of antibodies, which are responsible for antigen recognition, and can provide protection by blocking the function of their target antigen. However, recent developments in our understanding of the protection mediated by antibodies have highlighted the critical nature of the antibody constant, or Fc domain, in the biological activity of antibodies. The Fc domain allows antibodies to link the adaptive and innate immune systems, providing specificity to a wide range of innate effector cells. In addition, they provide a feedback loop to regulate the character of the immune response via interactions with B cells and antigen-presenting cells. Clarifies the different mechanisms of IgG activity at the level of the different model systems used, including human genetic, mouse, and in vitro Covers the role of antibodies in cancer, infectious disease, and autoimmunity and in the setting of monoclonal antibody therapy as well as naturally raised antibodies Color illustrations enhance explanations of the immune system

The key roles of the complement cascade and cellular Fcγ receptors in the innate and adaptive immune system are well documented. Recognition of soluble or cell-bound IgG-containing immune complexes by either of these two respective effector systems leads to a complex series of separate and non-overlapping inflammatory reactions and cytotoxic processes, each of which serves to remove or destroy opsonized microorganisms or targeted tumor cells. Alternatively, in autoimmune diseases these reactions mediate severe pathologies which are manifested in local or systemic inflammation as well as in tissue injury. For some time, it appeared that these two effector systems functioned independently and did not communicate; however, increasing evidence reveals synergy and feedback control between these two systems. Indeed, danger signals can alert one system leading to cross-communication and cooperation with the other to efficiently eliminate the threat. On the other hand, undesired and deleterious inflammation can be controlled by FcγR-mediated suppression of complement.