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2021 ◽  
Author(s):  
◽  
Sarrabeth Marie Stone

<p>Multiple Sclerosis (MS) is an immune-mediated disease of the central nervous system (CNS) which causes demyelination and damage to the neuronal axons. MS is a significant health problem in New Zealand, affecting 1 in 1400 people. One of the major cell types involved in MS and its animal model, experimental autoimmune encephalomyelitis (EAE), are the proinflammatory subsets of T helper (Th) cells. However, many other cell types are also involved, including macrophages (MΦ) and microglia (MG). MΦ and MG are considered to be important drivers of inflammation during MS; however there is also evidence that indicates these cells can also play a protective role. In the periphery, MΦ can be induced into several activation states. One of these activation states, type II activation, is a regulatory phenotype, producing increased IL-10 and decreased IL-12 compared to classical activation. In vitro type II activation is induced by ligating FcγR with immune complexes (IC) with concurrent stimulation with lipopolysaccharide. Previous research has shown that type II activated MΦ and type II-inducing treatments are protective in EAE.  MΦ activation state affects the way the Th response develops, with classically activated MΦ promoting a Th1 response and type II MΦ promoting a Th2 response. In the current study, the role of MΦ in T cell biasing is investigated further. Type II activated MΦ altered the Th1/Th2 dichotomy away from a Th1 response and towards a Th2 response, as demonstrated by decreased production of IFN-γ and increased levels of CD124. Also, in a novel finding, type II activated MΦ also increased the production of IL-17A from T cells. This study also aimed to elucidate the pathways involved in biasing of the T cell response by classical and type II MΦ by blocking or enhancing specific pathways. It was found that, while the level of IFN-γ (the prototypical Th1 cytokine) was largely dependent on the levels of IL-10 and IL-12, IL-17A and CD124 expression appeared to be independent of these two cytokines. Type II MΦ have decreased expression of CD40 and PD-L1, it was found that these pathways are not strongly involved in T cell biasing by type II MΦ.  While it is acknowledged that MG can be pathogenic and protective, the direct effect type II activating treatments have on MG is unknown. In order to investigate whether MG can also be type II activated, MG were isolated from the CNS of adult mice their phenotype under different activating condition was assessed. Under type II activating conditions MG produced less IL-12 and more IL-10, suggesting type II activation is occurring. In addition, in MG:T cell co-cultures, T cells cultured with classical or type II activated MG have similar, but not identical, profiles to T cells cultured with MΦ. Type II activated MΦ induced increases in CD124 and IL-17A from T cells, however, all MG activation states induced similar levels of IFN-γ.  To determine the effect of type II activating treatments in vivo bone marrow chimeric mice were created using mice congenic for CD45, which allow MG to be distinguished from invading cells. Treatment of mice with the IC before and during EAE results in decrease the incidence and severity of disease. IC treatments altered both the peripheral and the CNS immune environments. Despite inducing protection, IC treatments induced an increase in IL-17A in the peripheral immune system. In the brain, a population of resident cells that are CD45(int)CD11b positive, and are likely to be CNS associated MΦexpress decreased levels of MHC class II, suggesting a decreased ability to interact with T cells. Furthermore, parenchymal MG from the brains of IC treated animals have different levels of Iba1 compared to those from untreated animals, suggesting differential activation. Overall the data suggests that IC treatment induces a change in the activation state of CNS resident immune cells, that is likely to be protective in EAE.</p>


2021 ◽  
Author(s):  
◽  
Sarrabeth Marie Stone

<p>Multiple Sclerosis (MS) is an immune-mediated disease of the central nervous system (CNS) which causes demyelination and damage to the neuronal axons. MS is a significant health problem in New Zealand, affecting 1 in 1400 people. One of the major cell types involved in MS and its animal model, experimental autoimmune encephalomyelitis (EAE), are the proinflammatory subsets of T helper (Th) cells. However, many other cell types are also involved, including macrophages (MΦ) and microglia (MG). MΦ and MG are considered to be important drivers of inflammation during MS; however there is also evidence that indicates these cells can also play a protective role. In the periphery, MΦ can be induced into several activation states. One of these activation states, type II activation, is a regulatory phenotype, producing increased IL-10 and decreased IL-12 compared to classical activation. In vitro type II activation is induced by ligating FcγR with immune complexes (IC) with concurrent stimulation with lipopolysaccharide. Previous research has shown that type II activated MΦ and type II-inducing treatments are protective in EAE.  MΦ activation state affects the way the Th response develops, with classically activated MΦ promoting a Th1 response and type II MΦ promoting a Th2 response. In the current study, the role of MΦ in T cell biasing is investigated further. Type II activated MΦ altered the Th1/Th2 dichotomy away from a Th1 response and towards a Th2 response, as demonstrated by decreased production of IFN-γ and increased levels of CD124. Also, in a novel finding, type II activated MΦ also increased the production of IL-17A from T cells. This study also aimed to elucidate the pathways involved in biasing of the T cell response by classical and type II MΦ by blocking or enhancing specific pathways. It was found that, while the level of IFN-γ (the prototypical Th1 cytokine) was largely dependent on the levels of IL-10 and IL-12, IL-17A and CD124 expression appeared to be independent of these two cytokines. Type II MΦ have decreased expression of CD40 and PD-L1, it was found that these pathways are not strongly involved in T cell biasing by type II MΦ.  While it is acknowledged that MG can be pathogenic and protective, the direct effect type II activating treatments have on MG is unknown. In order to investigate whether MG can also be type II activated, MG were isolated from the CNS of adult mice their phenotype under different activating condition was assessed. Under type II activating conditions MG produced less IL-12 and more IL-10, suggesting type II activation is occurring. In addition, in MG:T cell co-cultures, T cells cultured with classical or type II activated MG have similar, but not identical, profiles to T cells cultured with MΦ. Type II activated MΦ induced increases in CD124 and IL-17A from T cells, however, all MG activation states induced similar levels of IFN-γ.  To determine the effect of type II activating treatments in vivo bone marrow chimeric mice were created using mice congenic for CD45, which allow MG to be distinguished from invading cells. Treatment of mice with the IC before and during EAE results in decrease the incidence and severity of disease. IC treatments altered both the peripheral and the CNS immune environments. Despite inducing protection, IC treatments induced an increase in IL-17A in the peripheral immune system. In the brain, a population of resident cells that are CD45(int)CD11b positive, and are likely to be CNS associated MΦexpress decreased levels of MHC class II, suggesting a decreased ability to interact with T cells. Furthermore, parenchymal MG from the brains of IC treated animals have different levels of Iba1 compared to those from untreated animals, suggesting differential activation. Overall the data suggests that IC treatment induces a change in the activation state of CNS resident immune cells, that is likely to be protective in EAE.</p>


Immunity ◽  
2021 ◽  
Author(s):  
Emilie V. Russler-Germain ◽  
Jisun Jung ◽  
Aidan T. Miller ◽  
Shannon Young ◽  
Jaeu Yi ◽  
...  

Author(s):  
Phillip A. Swanson ◽  
Marcelino Padilla ◽  
Wesley Hoyland ◽  
Kelly McGlinchey ◽  
Paul A. Fields ◽  
...  

Author(s):  
Astrid Herzum ◽  
Martina Burlando ◽  
Mattia Molle ◽  
Claudia Micalizzi ◽  
A. Parodi

We report the third case of lichen planus (LP) following COVID-19 BNT162b2 vaccination in a 59-year-old woman with previous LP. The reactivation of LP in patients with dormant LP, suggests possible vaccine-induced immune dysregulation. We suggest that the already described vaccine-induced up-regulation of Th1 response, may play a relevant role.


2021 ◽  
Vol 12 ◽  
Author(s):  
T. T. Guimarães ◽  
S. M. R. Gomes ◽  
R. A. A. C. Albuquerque ◽  
A. K. C. Lima ◽  
G. F. Braga ◽  
...  

Physical inactivity is one of the main causes of chronic diseases; however, strenuous exercise can induce immunosuppression. Several studies suggest that moderate amounts of exercise lead to a Th1 response, favoring the resolution of infections caused by intracellular microorganisms, while high volumes of exercise tend to direct the response to Th2, favoring infection by them. Leishmaniasis is a parasitic disease promoted by parasites of the Leishmania genus, with clinical manifestations that vary according to the species of the parasite and the immune response of the host. The experimental Leishmania major–BALB/C mouse model provides a good model for the resistance (Th1 response) or susceptibility (Th2 response) that determines the progression of this infection. The aim of this study was to evaluate the effect of aerobic training at different volumes on modulation of in vitro macrophage infection by L. major, as well as to assess the effect of high volume (HV) aerobic training on the development of L. major in vivo in BALB/c mice. Uninfected animals were submitted to various exercise volumes: none (SED), light (LV), moderate (MV), high (HV), very high (VHV), and tapering (TAP). The macrophages of these animals were infected by L. major and the LV and MV groups showed a decrease in the infection factor, while the VHV showed an increase in the infection factor, when treated with LPS. The cytokine concentration pattern measured in the supernatants of these macrophages suggested a predominant Th1 response profile in the LV and MV groups, while the Th2 profile predominated in the VHV and TAP groups. Groups of BALB/C mice infected with L. major were subjected to high volume (iHV) or non-periodized high volume (iNPHV) exercise or kept sedentary (iSED). The exercised animals suffered a significant increase in injuries caused by the parasites. The animals in the group submitted to high volume exercise (iHV) showed visceralization of the infection. These data strongly suggest that a very high volume of aerobic training increased the susceptibility of BALB/C mice to L. major infection, while moderate distribution of training loads promoted immunological balance, better controlling the infection by this parasite.


immuneACCESS ◽  
2021 ◽  
Author(s):  
PA Swanson ◽  
M Padilla ◽  
W Hoyland ◽  
K McGlinchey ◽  
PA Fields ◽  
...  

2021 ◽  
Vol 3 (3) ◽  
pp. 138-141
Author(s):  
Gilles R.G. Monif

Infectious Diseases Incorporated (IDI) is an infectious disease think-tank, established in 1973. Crohn’s disease (CD) is a chronic, recurrent disease of the gastrointestinal tract that has reached epidemic proportions within industrialized nations. CD is said to be without cure. Since 2003, therapeutic interventions have focused on disruption of the pro-inflammatory Th1 response against an unknown antigen. In 2015, the Hruska Postulate was introduced and, in so doing, explained how, in the absence of acquired immunity, newborn infection by Mycobacterium avium subspecies paratuberculosis could cause fixation of the immune system’s Th1 response against the organism. The Hruska Postulate was utilized to answer all the documented epidemiological facts embedded in the natural history of Crohn’s disease and, in particular, why breastfeeding confers protection against the future development of Crohn’s disease. It is Infectious Diseases Incorporated’s (IDI) stated opinion that Crohn’s disease is both preventable and curable if treated appropriately in its early stages.


Author(s):  
Fabiana Nabarro Ferraz ◽  
Franciele Karina Da Veiga ◽  
Denise Lessa Aleixo ◽  
Silvana Marques De Araújo

The use of biotherapics as an intervention in experimental models of infection is a possible means to understand the effects of these medications [1-3]. This study evaluated the immunological and parasitological effects of biotherapics that were prepared from mouse or rabbit serum uninfected (MUI or RUI groups) or chronically infected with T. cruzi (MI or RI groups), dynamization 13cH. Male Swiss mice, 28 days of age were infected with T. cruzi-Y strain and treated with the different biotherapics diluted in water (1mL/100mL). The study was approved by the Ethics Committee for Experiments in Animals-UEM (protocol no. 080/2012). Using biotherapics made with mouse serum, MUI group exhibited good outcome with a pronounced Th1 response that was attributable to a reduction of IL-4 concentrations and decrease in IL-17 concentrations compared with the control group. However, this cytokine balance was not sufficient to promote decreased parasitemia in treated animals, likely because of a decrease in IFN-gama, thus hindering a more effective beneficial Th1 response. In contrast, the MI group presented a pronounced Th2 response that was attributable to increase in IL-4 and decrease in IFN-gama concentration compared to control group. MI group exhibited the worst outcome where the cytokine balance suppressed the immune response to T. cruzi in murine infection, resulting in a significant increased parasitemia and decreased survival time. Using biotherapics made with rabbit serum, RUI group exhibited the best outcome, including decreased parasitemia, with pronounced Th1 response that was attributable to decrease in IL-4 concentrations, with no changes in TNF-alpha and IFN-gama, associated to decrease in IL-17 compared to control group. In contrast, RI group did not exhibit alterations in parasitemia but a pronounced Th2 response that was attributable to increase in IL-4 concentration, with no changes in TNF-alpha and IFN-gama, associated to decrease in IL-17 compared to control group. Results show that biotherapics that were prepared from mouse or rabbit serum uninfected or chronically infected with T. cruzi differentially modulate the immune system in mice infected with this protozoan. Also, results provide evidence that biotherapics prepared with serum from healthy animal performed better than one made with serum from infected animal. In the same way biotherapics prepared with serum from resistant specie performed better than one made with serum from susceptible specie.


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