Sympathetic Nerves and Innate Immune System in the Spleen: Implications of Impairment in HIV-1 and Relevant Models

Abstract

The immune and sympathetic nervous systems are major targets of human, murine and simian immunodeficiency viruses (HIV-1, MAIDS, and SIV, respectively). The spleen is a major reservoir for these retroviruses, providing a sanctuary for persistent infection of myeloid cells in the white and red pulps. This is despite the fact that circulating HIV-1 levels remain undetectable in infected patients receiving combined antiretroviral therapy. These viruses sequester in immune organs, preventing effective cures. The spleen remains understudied in its role in HIV-1 pathogenesis, despite it hosting a quarter of the body’s lymphocytes and diverse macrophage populations targeted by HIV-1. HIV-1 infection reduces the white pulp, and induces perivascular hyalinization, vascular dysfunction, tissue infarction, and chronic inflammation characterized by activated epithelial-like macrophages. LP-BM5, the retrovirus that induces MAIDS, is a well-established model of AIDS. Immune pathology in MAIDs is similar to SIV and HIV-1 infection. As in SIV and HIV, MAIDS markedly changes splenic architecture, and causes sympathetic dysfunction, contributing to inflammation and immune dysfunction. In MAIDs, SIV, and HIV, the viruses commandeer splenic macrophages for their replication, and shift macrophages to an M2 phenotype. Additionally, in plasmacytoid dendritic cells, HIV-1 blocks sympathetic augmentation of interferon-β (IFN-β) transcription, which promotes viral replication. Here, we review viral–sympathetic interactions in innate immunity and pathophysiology in the spleen in HIV-1 and relevant models. The situation remains that research in this area is still sparse and original hypotheses proposed largely remain unanswered.

Bidirectional crosstalk between the peripheral nervous system and lymphoid tissues/organs

“…The PNS communicates specifically with the immune system according to local interactions/conditions ( 34 , 35 ). For example, the main immune organs (e.g., bone marrow, thymus, spleen, and lymph nodes) are supplied with an autonomic efferent (mainly sympathetic) innervation and afferent sensory innervation, and both classic (catecholamines and acetylcholine (ACh)) and peptide neurotransmitters are probably involved in this type of neuroimmune modulation ( 36 – 38 ). However, despite these above-mentioned studies that indicate the occurrence of functional interconnections between the immune and nervous systems, data available on the mechanisms of this bidirectional crosstalk between the PNS and immune system are frequently incomplete and not always focused on their relevance for neuroimmune modulations in neuroimmunological, infectious, immunological disorders/diseases.…”