Fig 4 - available via license: Creative Commons Attribution 4.0 International
Content may be subject to copyright.
Small intestine inflammation is prominent with Nef exposure and is reduced by propranolol coadministration. (A) Representative photos of Hematoxylin & Eosin staining of the small intestine at (40x). The staining clearly demonstrates the Peyer's Patches (PP) in the small intestine in the Nef-only group. (B) Immunofluorescence of CD68+ cells (shown in red) and iNOS (shown in green) in the small intestine, blue is DAPI. (C, D) Quantitative results, number of cells counted per high power field (HPF), from the double immunofluorescence evidenced upregulation of CD68+ cells and iNOS in the Nef-only group while CD68+ cells and iNOS remained at normal levels in the Nef + propranolol group. (E) Measurement of PP in the small intestine shows that Nef causes enlargement; the effect is abrogated by propranolol. Scale bar indicates 35um. All p-values were two-tailed and statistical significances were defined as � p-value <0.05, �� p-value <0.01, ��� p-values <0.001, and ���� p-values <0.0001. https://doi.org/10.1371/journal.pone.0259446.g004
Source publication
Combination antiretroviral therapy (cART) targets viral replication, but early viral protein production by astrocytes may still occur and contribute to the progression of HIV-1 associated neurocognitive disorders and secondary complications seen in patients receiving cART. In prior work with our model, astrocytic HIV-1 Nef expression exhibits neuro...
Contexts in source publication
Context 1
... a follow up, we proceeded to analyze the GI tissue and test if propranolol treatment could abrogate the effects of Nef. Similar to prior findings [10] , Fig 4(A) shows disruption of the standard architecture of the small intestine (SI) after Nef treatment compared to the naïve and propranolol-only groups. The Nef-only group shows atrophy and disrupted morphology of the ileal villi, disruption of the muscle layer, and increased infiltration of immune cells . ...
Context 2
... of Nef. Similar to prior findings [10] , Fig 4(A) shows disruption of the standard architecture of the small intestine (SI) after Nef treatment compared to the naïve and propranolol-only groups. The Nef-only group shows atrophy and disrupted morphology of the ileal villi, disruption of the muscle layer, and increased infiltration of immune cells . Fig 4(B) depicts merged immunostaining in the SI with the macrophage marker, CD68 (red) and iNOS (green) (see S2 Fig for individual color images). Quantification of CD68 (Fig 4C) shows a 5-fold increase in the group expressing Nef in the hippocampus, while systemic administration of propranolol significantly reduces that increase by ...
Context 3
... 4(B) depicts merged immunostaining in the SI with the macrophage marker, CD68 (red) and iNOS (green) (see S2 Fig for individual color images). Quantification of CD68 (Fig 4C) shows a 5-fold increase in the group expressing Nef in the hippocampus, while systemic administration of propranolol significantly reduces that increase by 50%. ...
Context 4
... , Fig 4(D) shows a significant 8-fold increase of iNOS expression by Nef. Propranolol alone or co-administered with Nef results in no significant increase over baseline (naïve). ...
Context 5
... Patches are lymphoid tissue found in the small intestine. Fig 4(E) shows that the Nef-only group demonstrated significant inflammation shown by an average PP diameter measuring of 0.6mm. This inflammation was greatly reduced it by propranolol coadminstration-mean diameter of PP in the Nef + propranolol group was 0.2mm, significantly less. ...
Citations
... IL-1β and TNF-α are proin ammatory cytokines secreted by monocytes. Their augment may be due to the persistent stimulation of HIV regulatory proteins by HIV antigens, resulting in an increased monocyte release of IL-1β and TNF-α[19,20]. IL-7 secreted by bone marrow stromal cells promotes the development and differentiation of T cells, and HIV replication in infected patients is maintained by IL-7[21]. IL-6 can activate latent viruses and induce them to replicate in vitro[22]. ...
Objective
Human immunodeficiency virus type 1 (HIV-1) infection disturbs the balance of CD4⁺ T cells and monocytes in the immune system. In the early stage of infection, the virus stimulates the activation and proliferation of immune cells, induces the release of cytokines, destroys CD4⁺ T cells, and accelerates HIV-1 replication and AIDS progression. It is essential to explore cytokine changes after HIV-1 infection and further understand the underlying mechanism of HIV infection.
Materials and methods
In this study, we enrolled 38 HIV-infected subjects and 30 healthy subjects. We measured and compared CD4⁺ T cell counts, the tropism of HIV and the serum cytokine levels in different groups.
Results
Our results showed significantly higher serum levels of IL-1β, IL-2, IL-4, IL-7, IL-10, IL-17, IFN-γ, and TNF-α in HIV-infected patients. Higher levels of IL-6 and IL-17 were observed in the < 200/mL CD4⁺ T cell count group, and higher levels of IL-2 were observed in the CCR5-tropic HIV strain group.
Conclusion
In conclusion, we found that HIV infection-induced activation of the immune system. IL-6 and IL-17 may predict the severity of HIV disease and regulate HIV infection. The level of IL-2 depended on the type of virus strain.
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.
