scholarly journals Immunopathogenesis of Aspergillosis

2021 ◽  
Author(s):  
Shreya Singh ◽  
Rimjhim Kanaujia ◽  
Shivaprakash M Rudramurthy

Aspergillus species are ubiquitous saprophytes and opportunistic pathogens causing wide spectrum of diseases in humans depending on the host immune status. Following pathogen entry, various soluble bronchopulmonary factors enhance conidial clearance. However, due to virulence factors and poor host immune response Aspergillus conidia bind and damage the airway epithelium. The host immune cells like neutrophils and macrophages recognise Aspergillus spp. through various pathogen recognition receptors and form reactive oxygen species which mediate conidial killing. Neutrophils also attack extracellular hyphae by oxidative attack, non-oxidative granule proteins and neutrophil extracellular traps. In case of adaptive immunity, Th1 cells are crucial sources of IFN-γ mediated protective immunity. The Th17 also display a highly pro-inflammatory which is counterbalanced by a Treg cell. B cells and antibodies also enhance fungal clearance although excessive IgE production may result in atopy. The immune responses are influenced by changes in production of short-chain fatty acids by the gut microbiome which primes cells toward Th2 responses, and this is synchronized by the Innate lymphoid cells. This review provides comprehensive knowledge of various virulence factors of Aspergillus, antifungal host defences including innate and humoral immune response and regulation of host immunity by microbiome.

Viruses ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 369
Author(s):  
Jianglong Li ◽  
Kui Fang ◽  
Zhenxiang Rong ◽  
Xinxin Li ◽  
Xujiao Ren ◽  
...  

Pseudorabies (PR), caused by pseudorabies virus (PRV), is an acute and febrile infectious disease in swine. To eradicate PR, a more efficacious vaccine needs to be developed. Here, the gE/gI- and TK/gE/gI-gene-deleted recombinant PRV (rGXΔgE/gI and rGXΔTK/gE/gI) are constructed through CRISPR/Cas9 and Cre/Lox systems. We found that the rGXΔTK/gE/gI was safer than rGXΔgE/gI in mice. Additionally, the effects of rGXΔgE/gI and rGXΔTK/gE/gI were further evaluated in swine. The rGXΔgE/gI and rGXΔTK/gE/gI significantly increased numbers of IFN-γ-producing CD4+ and CD8+ T-cells in swine, whereas there was no difference between rGXΔgE/gI and rGXΔTK/gE/gI. Moreover, rGXΔgE/gI and rGXΔTK/gE/gI promoted a PRV-specific humoral immune response. The PRV-specific humoral immune response induced by rGXΔgE/gI was consistent with that caused by rGXΔTK/gE/gI. After the challenge, swine vaccinated with rGXΔgE/gI and rGXΔTK/gE/gI showed no clinical signs and viral shedding. However, histopathological detection revealed that rGXΔgE/gI, not rGXΔTK/gE/gI, caused pathological lesions in brain and lung tissues. In summary, these results demonstrate that the TK/gE/gI-gene-deleted recombinant PRV was safer compared with rGXΔgE/gI in swine. The data imply that the TK/gE/gI-gene-deleted recombinant PRV may be a more efficacious vaccine candidate for the prevention of PR.


2012 ◽  
Vol 49 (4) ◽  
pp. 201-210 ◽  
Author(s):  
E. Dvorožňáková ◽  
M. Kołodziej-Sobocińska ◽  
Z. Hurníková

AbstractTrichinella spiralis infection induces a host cell-mediated and humoral response. The role of T and B lymphocytes in the immune response of mice reinfected with 2 × 400 T. spiralis larvae was studied in relation to the parasite burden. BALB/c mice were infected on days 0 and 60 and immunological parameters were examined within a period of 180 days. In comparison with a single T. spiralis infection, T- and B-lymphocytes in reinfected mice responded by a significant increase in the proliferative activity during 10 days after reinfection. At the same time, the percentages of CD4+ T-cells of reinfected mice were also increased. In contrast, the CD8+ T-cell numbers were significantly reduced almost 30 days after reinfection. High concentration of serum IFN-γ lasted till the end of the experiment. The IL-5 level was increased only for 2 weeks after reinfection, followed by its decrease. Kinetics of specific anti-Trichinella immunoglobulins IgG2a was not affected with reinfection, but specific antibodies IgG1 significantly increased after reinfection and persisted elevated till the end of the experiment. Lower numbers of adults (69.2 % reduction) in the small intestine and 72.3 % reduction in muscle larvae were found after reinfection. Stimulation of the host immune response — the increased activity of CD4+ T lymphocytes and high levels of IFN-γ and specific IgG1 after reinfection, contributed to the reduction of the parasite burden.


2004 ◽  
Vol 72 (7) ◽  
pp. 3925-3931 ◽  
Author(s):  
K. A. Eaton ◽  
S. M. Logan ◽  
P. E. Baker ◽  
R. A. Peterson ◽  
M. A. Monteiro ◽  
...  

ABSTRACT The goal of this study was to determine whether Helicobacter pylori lipopolysaccharide (LPS) O-chain polysaccharide contributes to gastritis in a mouse model. C57BL/6J or C57BL/6-Prkdcscid (severe combined immunodeficient [SCID]) mice were inoculated with H. pylori strain SS1 or SS1::0826kan, in which a β-1,4-galactosyltransferase (HP0826), an LPS biosynthetic enzyme, had been disrupted. H. pylori strain SS1::0826kan expresses truncated LPS lacking O chain. Recipient SCID mice were given C57BL/6J splenocytes by intraperitoneal injection. Bacterial colonization, gastric lesions (gastritis, neutrophilic infiltration, and gastric epithelial metaplasia), cellular (delayed-type hypersensitivity) and humoral immune responses to H. pylori sonicate, and gastric gamma interferon (IFN-γ) mRNA expression were quantified. Recipient SCID mice colonized by H. pylori strain SS1 developed extensive gastritis with loss of normal fundic gland morphology. In contrast, gastric mucosa of recipient SCID mice colonized by H. pylori strain SS1::0826kan was not statistically distinguishable from that of uninfected recipient mice. Delayed-type hypersensitivity and humoral immune responses were detected in infected mice inoculated with wild-type SS1, but not with SS1::0826kan. IFN-γ transcription was lower in mice infected with SS1::0826kan than in mice infected with SS1. In this model of rapidly progressive gastritis due to H. pylori, the O chain contributed to the extent of gastritis and to the host immune response. These data support a role for H. pylori LPS O chain in direct induction of the host immune response leading to gastritis and gastric damage and are in contrast to protein antigens, such as urease and cag products which do not contribute to gastritis in mice.


2020 ◽  
Author(s):  
Mahsa Rabienia ◽  
Zahra Roudbari ◽  
Ali Ghanbariasad ◽  
Abbas Abdollahi ◽  
Alireaza Molazadeh ◽  
...  

Abstract Background: Nowadays, the prevention of parasitic diseases including leishmaniasis is one of the health concerns in the world, and cutaneous leishmaniasis is the most common type of these diseases. So far, no drug or vaccine has been approved for definitive treatment of this disease.Methods: In this study, the recombinant lentiviral vaccine containing a new multi-epitope of KMP11 and HASPB of the Leishmania major (L. major) was synthesized that had previously been designed in-silico. The designed multi-epitope was subcloned into the pCDH513 lentiviral vector, and the recombinant lentiviral multi-epitope vaccine (rLV-multi-epitope) was synthesized in the HEK293T cell by the packaging vectors. Also, the Western Blotting method was used to confirm the gene expression. Then, the rLV-multi-epitope vaccine was injected twice, along with two control groups, PBS, and rLV-empty to immunize the BALB /c mice. Twenty-one days after the second injection, the splenocytes of the mice were is­­­­olated and stimulated with the Leishmania lysate.Results: The results of the enzyme-linked immunoassay (ELISA) test not only showed the titer of IFN-γ and IL-4 was increased in the immunized group compared to the controls, but also indicated that the ratio of IFN-γ to IL-4 cytokines in the main group was increased significantly. As a result, the Th1 response was generated in the main group. Moreover, the humoral immune response was assessed and the results showed that the ratio of IgG2a to IgG1 antibody in the sera of the immunized mice was increased compared to the control groups. Also, the ratio of IgG2a to IgG1 was increased in the main group. Therefore, the humoral immune response was increased, which can also have a positive effect on increasing the Th1 response.Conclusions: Our results showed that immunization by the new rLV-multi-epitope vaccine could stimulate the immune system towards the Th1 through increasing the IFN-γ production.


1997 ◽  
Vol 186 (3) ◽  
pp. 385-391 ◽  
Author(s):  
Balaji Balasa ◽  
Caishu Deng ◽  
Jae Lee ◽  
Linda M. Bradley ◽  
Dyana K. Dalton ◽  
...  

Experimental autoimmune myasthenia gravis (EAMG) is an animal model of human myasthenia gravis (MG). In mice, EAMG is induced by immunization with Torpedo californica acetylcholine receptor (AChR) in complete Freund's adjuvant (CFA). However, the role of cytokines in the pathogenesis of EAMG is not clear. Because EAMG is an antibody-mediated disease, it is of the prevailing notion that Th2 but not Th1 cytokines play a role in the pathogenesis of this disease. To test the hypothesis that the Th1 cytokine, interferon (IFN)-γ, plays a role in the development of EAMG, we immunized IFN-γ knockout (IFN-gko) (−/−) mice and wild-type (WT) (+/+) mice of H-2b haplotype with AChR in CFA. We observed that AChR-primed lymph node cells from IFN-gko mice proliferated normally to AChR and to its dominant pathogenic α146–162 sequence when compared with these cells from the WT mice. However, the IFN-gko mice had no signs of muscle weakness and remained resistant to clinical EAMG at a time when the WT mice exhibited severe muscle weakness and some died. The resistance of IFN-gko mice was associated with greatly reduced levels of circulating anti-AChR antibody levels compared with those in the WT mice. Comparatively, immune sera from IFN-gko mice showed a dramatic reduction in mouse AChR-specific IgG1 and IgG2a antibodies. However, keyhole limpet hemocyanin (KLH)–priming of IFN-gko mice readily elicited both T cell and antibody responses, suggesting that IFN-γ regulates the humoral immune response distinctly to self (AChR) versus foreign (KLH) antigens. We conclude that IFN-γ is required for the generation of a pathogenic anti-AChR humoral immune response and for conferring susceptibility of mice to clinical EAMG.


2005 ◽  
Vol 79 (5) ◽  
pp. 2900-2909 ◽  
Author(s):  
Lisa Lindesmith ◽  
Christine Moe ◽  
Jacques LePendu ◽  
Jeffrey A. Frelinger ◽  
John Treanor ◽  
...  

ABSTRACT Little is known about the immune response to noroviruses. To elucidate the immunobiology of norovirus infection in humans, 15 volunteers were challenged with Snow Mountain virus (SMV), a genogroup 2 norovirus. We assessed the cellular and humoral immune response and infection by analyzing stool, serum, saliva, and peripheral blood mononuclear cell (PBMC) responses pre- and postchallenge. In contrast to Norwalk virus (NV), SMV infection was not dependent upon blood group secretor status. Nine of 15 volunteers were infected and showed a ≥4-fold increase over the prechallenge anti-SMV serum immunoglobulin G (IgG) titer, mostly subclass IgG1. Although serum IgG elicited by SMV infection was cross-reactive with Hawaii virus (HV), another genogroup 2 norovirus, salivary IgA was less cross-reactive. Neither SMV-elicited serum IgG nor salivary IgA cross-reacted with NV, a genogroup 1 norovirus. Significant increases in serum gamma interferon (IFN-γ) and IL-2, but not IL-6 or IL-10, were noted on day 2 postchallenge. For the majority of volunteers, both infected and uninfected, PBMCs stimulated with norovirus virus-like particles secreted IFN-γ and other Th1 cytokines, suggesting previous norovirus exposure in most volunteers. Like the IgG antibodies, the SMV-activated T cells were cross-reactive with HV but not NV. IFN-γ production was dependent upon CD4+ cells, consistent with a predominant, but not exclusive, Th1 response. To our knowledge, this is the first report characterizing T-cell and cytokine responses following live norovirus challenge.


2017 ◽  
Vol 63 (4) ◽  
pp. 312-320 ◽  
Author(s):  
Ling Guo ◽  
Lei Xu ◽  
Tao Wu ◽  
Shulin Fu ◽  
Yinsheng Qiu ◽  
...  

Haemophilus parasuis can cause a severe membrane inflammation disorder. It has been documented that superoxide dismutase (SOD) is a potential target to treat systemic inflammatory diseases. Therefore, we constructed an experimental H. parasuis subunit vaccine SOD and determined the protective efficacy of SOD using a lethal dose challenge against H. parasuis serovar 4 strain MD0322 and serovar 5 strain SH0165 in a mouse model. The results demonstrated that SOD could induce a strong humoral immune response in mice and provide significant immunoprotection efficacy against a lethal dose of H. parasuis serovar 4 strain MD0322 or serovar 5 strain SH0165 challenge. IgG subtype analysis indicated SOD protein could trigger a bias toward a Th1-type immune response and induce the proliferation of splenocytes and secretion of IL-2 and IFN-γ of splenocytes. In addition, serum in mice from the SOD-immunized group could inhibit the growth of strain MD0322 and strain SH0165 in the whole-blood killing bacteria assay. This is the first report that immunization of mice with SOD protein could provide protective effect against a lethal dose of H. parasuis serovar 4 and serovar 5 challenge in mice, which may provide a novel approach against heterogeneous serovar infection of H. parasuis in future.


2015 ◽  
Vol 35 (11) ◽  
pp. 844-849 ◽  
Author(s):  
Bin Ji ◽  
Ting-Ting Sun ◽  
Zhi-Liang Ma ◽  
Qiong-Fen Lu ◽  
Wen-Li Hu ◽  
...  

Parasitology ◽  
2004 ◽  
Vol 129 (5) ◽  
pp. 563-570 ◽  
Author(s):  
V. R. A. PEREIRA ◽  
V. M. B. LORENA ◽  
A. P. GALVAO DA SILVA ◽  
E. M. COUTINHO ◽  
E. D. SILVA ◽  
...  

In previous studies, we demonstrated that CRA and FRA recombinant proteins, used for diagnosis of Chagas' disease, elicited a humoral immune response in susceptible and resistant mice. To understand better the immune response to these proteins, we have evaluated, the cellular immune response in CRA- and in FRA-immunized BALB/c and C57BL/6 mice. A specific cellular lymphoproliferative response was observed in both strains of mice. Spleen cell cultures mainly from CRA-immunized C57BL/6 and FRA-immunized BALB/c mice produced high levels of IFN-γ, indicating the induction of a Type 1 immune response. Regarding the T cell subsets, CD4+T cells were the major source of IFN-γ in CRA- and FRA-immunized mice. These results suggest that CRA and FRA are important immunogens in inducing a Type 1 immune response and that they may be considered as potential vaccine antigens.


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