Crit Rev Immunol
-
The pandemic caused by the SARS-CoV-2 has made new treatments a goal for the scientific community. One of these treatments is Ivermectin. Here we discuss the hypothesis of dysbiosis caused by the use of Ivermectin and the possible impacts on neuroinflammatory diseases after the end of the pandemic.
-
Coronavirus disease 2019 (COVID-19) consists of a severe involvement of the lower respiratory tract leading to an acute respiratory syndrome. But there exist other infectious respiratory syndromes that have the same initial respiratory symptoms, show similar pattern in the size of the antigenic proteins and release comparable cytokines pathways, but with an unlike response magnitude. Here we propose that COVID-19 disease wrong response in the host immune system can be explained in the perspective of the antigen viral size. ⋯ The sustained infected cells lysis overfeeds high levels of viral proteins < 70 kDa, increases B-cell activation and, in the shift from a Th1 to a Th2 immune response, can trigger a cytokine storm. The continuous BCR activation increases IL-10 release that can lead to cytokine storm, apoptosis, and immune paralysis. Here, we propose a new vaccine design using the polymerization of viral antigens that could be ready in short time, would be cheap and easy to develop because it is based on classic technologies available in every country, is safe because it does not employ genetic material, and would able to promote long-lasting B-cell immune memory and IgG2a production.
-
Review
Dimethyl fumarate modulation of immune and antioxidant responses: application to HIV therapy.
The persistence of chronic immune activation and oxidative stress in human immunodeficiency virus (HIV)-infected, antiretroviral drug-treated individuals are major obstacles to fully preventing HIV disease progression. The immune modulator and antioxidant dimethyl fumarate (DMF) is effective in treating immune-mediated diseases and it also has potential applications to limiting HIV disease progression. Among the relevant effects of DMF and its active metabolite monomethyl fumarate (MMF) are induction of a Th1 to Th2 lymphocyte shift, inhibition of pro-inflammatory cytokine signaling, inhibition of NF-κB nuclear translocation, inhibition of dendritic cell maturation, suppression of lymphocyte and endothelial cell adhesion molecule expression, and induction of the Nrf2-dependent antioxidant response element (ARE) and effector genes. ⋯ In addition, DMF and MMF limit HIV infection in macrophages in vitro, albeit by unknown mechanisms. Finally, DMF and MMF also suppress neurotoxin production from HIV-infected macrophages, which drives CNS neurodegeneration. Thus, DMF might protect against systemic and CNS complications in HIV infection through its effective suppression of immune activation, oxidative stress, HIV replication, and macrophage-associated neuronal injury.
-
The purpose of immunology is simple. Cure or prevent disease. M1/M2 is useful because it is simple. ⋯ And, these diseases are often associated with (or caused by) M1- or M2- type responses that were formerly useful for fighting infections, but now are inappropriate in our increasingly "germ-free" societies. In turn, there is considerable potential for modulating M1 or M2 Innate responses in modern diseases to achieve better health. Finally, since M1 and Th1 (or M2 and Th2) often work in concert to produce characteristic immune responses and disease pathologies, it is recommended that Immune Type 1 or 2 (IT1, IT2) would be a simpler and unifying terminology going forward.
-
Recognition of the pathogen-associated molecular pattern (PAMP) by host Toll-like receptors (TLR) is an important component of the innate immune response for countering against invading viruses, bacteria, and fungi. Upon PAMP recognition, the TLR induces intracellular signaling cascades that involve adapter, signalosome, and transcription factor complexes and result in the production of both pro- and anti-inflammatory cytokines and chemokines. An inflammatory response for a short duration can be beneficial because it helps to clear the infectious agent. ⋯ Therefore, fine control of inflammation in the TLR pathway is highly desirable for effective host defense. In this article, we review intrinsic control mechanisms that include a balance between pro-inflammatory and anti-inflammatory cytokines and chemokines, production of host effectors, and regulation at the level of adapter, signalosome, and transcription factor complexes in the TLR pathways. We also discuss how understanding of the TLR signaling steps leads to the development of small-molecule drugs that can interfere with the formation of active adapter, signalosome, and adapter complexes.