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Much is known about the natural history of syphilis; however, less is known about the immune response against it, and even less is known about people living with HIV (PLWH). Due to the lack of an animal model to study host-pathogen interactions, it remains unclear how the host eliminates the bacteria. Here, we attempt to elucidate the immune response against infection by summarizing all the reported data in a systematic review. We found that only seven papers included PLWH, and they did not accurately describe the immune response against Treponema pallidum since only lymphopenia was reported upon coinfection. On the other hand, at least sixteen papers described the host-pathogen interaction in individual cell populations. Using this information, we established the kinetics of the immune response against syphilis and hypothesized how CD4+ T cells, such as Th17 and T rex cells, worsen the progression of the disease in PLWH through their hallmark cytokines, IL-10 and IL-17, and how these two cytokines may play important roles as biomarkers. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB), primarily caused by Mycobacterium tuberculosis (M. tb), remains a widespread fatal health issue that becomes significantly detrimental when coupled with HIV. This study explores the host's innate and adaptive immune system response to TB in HIV immunocompromised patients, highlighting the significant role of CD8+ T cells. While the crucial role of macrophages and cytokines, like TNF-α and IFN-γ, in managing the host's immune response to M. tb is examined, the emphasis is on the changes that occur as a result of HIV coinfection. With the progression of HIV infection, the primary source of IFN-γ changes from CD4+ to CD8+ T cells, especially when latent TB advances to an active state. This study sheds light on the necessity of developing new preventative measures such as vaccines and new treatment approaches to TB, especially for immunocompromised patients, who are at a higher risk of life-threatening complications due to TB-HIV coinfection. [ABSTRACT FROM AUTHOR]

Human immunodeficiency virus (HIV) is a major cause of death worldwide. Without appropriate antiretroviral therapy, the infection can develop into acquired immunodeficiency syndrome (AIDS). AIDS leads to the dysregulation of cell-mediated immunity resulting in increased susceptibility to opportunistic infections and excessive amounts of inflammatory cytokines. HIV-positive individuals also demonstrate diminished glutathione (GSH) levels which allows for increased viral replication and increased pro-inflammatory cytokine release, further contributing to the high rates of mortality seen in patients with HIV. Adequate GSH supplementation has reduced inflammation and slowed the decline of CD4+ T cell counts in HIV-positive individuals. We aim to review the current literature regarding the role of GSH in cell-mediated immune responses in individuals with HIV- and AIDS-defining illnesses. [ABSTRACT FROM AUTHOR]

The development of new strategies to achieve a functional cure for HIV remains a priority. We tested a novel HIV therapeutic vaccine using unmodified mRNA (TMEP-B) and mRNA modified by 1-methyl-3′-pseudouridylyl (TMEP-Bmod) expressing both a multiepitopic sequences from Gag, Pol, and Nef proteins, including different CD4 and CD8 T-cell epitopes functionally associated with HIV control in transfected monocyte-derived dendritic cells (MDDCs) obtained from HIV infected patients. In vitro assays were used to test the mRNAs alone and in combination with immunomodulator agents, such as the TLR-7 agonist Vesatolimod and the PD-1 antagonist Nivolumab to try to improve HIV-specific cellular immune responses. Combining the mRNAs with the immunomodulators enhanced HIV-specific T-cell responses, together with the secretion of IFNγ, IP10, MIP-1α, and MIP-1β, which are fundamental mediators of viral control. Our data suggest that the mRNA vaccine prototypes TMEP-B and TMEP-Bmod, when combined with Vesatolimod and/or Nivolumab, could achieve functional cure for patients with HIV. [ABSTRACT FROM AUTHOR]