The Host Immune Response to Clostridium Difficile and the Immunomodulatory Effects of Probiotic Bacteria in Vitro

An increasing number of antiviral agents are presently in various stages of development and testing, and an increasing number have recently been licensed for use in humans. These drugs have been used extensively to treat viral infections in immunocompromised individuals, and these studies indicate that for many antiviral agents the response to therapy is highly dependent on the integrity of the underlying host immune response. In particular, the response to zidovudine, acyclovir and ganciclovir in persons with HIV-1 infection is highly dependent upon CD4 number, which can be considered a surrogate marker for the state of host immune function in these subjects. Responses to interferons likewise can be shown to depend on the host immune response, with responses due to both direct antiviral effects of this agent as well as immunomodulatory effects mediated through interferon-induced upregulation of HLA molecule expression.

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Unravelling some mysteries of porcine respiratory and reproductive syndrome virus (PRRSV) infections: new insights from modelling studies

Proceedings of the British Society of Animal Science ◽

10.1017/s1752756200028696 ◽

2009 ◽

Vol 2009 ◽

pp. 30-30

Author(s):

A Doeschl-Wilson ◽

I Kyriazakis ◽

L Galina-Pantoja

Keyword(s):

Immune Response ◽

Host Immune Response ◽

Growing Pigs ◽

Modelling Studies ◽

Porcine Respiratory ◽

Insight Into

Porcine reproductive and respiratory syndrome (PRRS) is an endemic pig disease in most European countries, causing respiratory distress, fever and growth reductions in growing pigs and increased litter mortality in sows. The disease is characterised by exceptionally long-term viral persistence within the host, a weak innate host immune response and delayed adaptive host immune response, and large between animal variation in the immune response (Murtaugh et al., 2004). Although numerous in-vitro and in-vivo studies produced valid insight into the fine details of the virus dynamics and its interaction with the host’s immune response, several fundamental questions concerning the role of diverse immune components and host genetics remain unanswered. In this study mathematical models were developed to investigate the role of diverse processes caused by the virus or the immune response on the infection characteristics.

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Isolation and characterization of porcine macrophages and their inflammatory and fusion responses in different stiffness environments

Biomaterials Science ◽

10.1039/d1bm00746g ◽

2021 ◽

Author(s):

Vijaykumar Meli ◽

Ryan Donahue ◽

Jarrett M Link ◽

Jerry C Hu ◽

Kyriacos A. Athanasiou ◽

...

Keyword(s):

Tissue Engineering ◽

Immune Response ◽

Medical Devices ◽

Host Immune Response ◽

In Vitro Studies ◽

Essential Step ◽

Isolation And Characterization

Evaluating the host immune response to biomaterials is an essential step in the development of medical devices and tissue engineering strategies. To aid in this process, in vitro studies, whereby...

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The Polysaccharide Capsule of Campylobacter jejuni Modulates the Host Immune Response

Infection and Immunity ◽

10.1128/iai.01008-12 ◽

2012 ◽

Vol 81 (3) ◽

pp. 665-672 ◽

Cited By ~ 46

Author(s):

Alexander C. Maue ◽

Krystle L. Mohawk ◽

David K. Giles ◽

Frédéric Poly ◽

Cheryl P. Ewing ◽

...

Keyword(s):

Immune Response ◽

Campylobacter Jejuni ◽

Diarrheal Disease ◽

Host Immune Response ◽

Interleukin 17 ◽

Wild Type ◽

Content Type ◽

Polysaccharide Capsule ◽

Colonization Model

ABSTRACTCampylobacter jejuniis a major cause of bacterial diarrheal disease worldwide. The organism is characterized by a diversity of polysaccharide structures, including a polysaccharide capsule. MostC. jejunicapsules are known to be decorated nonstoichiometrically with methyl phosphoramidate (MeOPN). The capsule ofC. jejuni81-176 has been shown to be required for serum resistance, but here we show that an encapsulated mutant lacking the MeOPN modification, anmpnCmutant, was equally as sensitive to serum killing as the nonencapsulated mutant. A nonencapsulated mutant, akpsMmutant, exhibited significantly reduced colonization compared to that of wild-type 81-176 in a mouse intestinal colonization model, and thempnCmutant showed an intermediate level of colonization. Both mutants were associated with higher levels of interleukin 17 (IL-17) expression from lamina propria CD4+cells than from cells from animals infected with 81-176. In addition, reduced levels of Toll-like receptor 4 (TLR4) and TLR2 activation were observed followingin vitrostimulation of human reporter cell lines with thekpsMandmpnCmutants compared to those with wild-type 81-176. The data suggest that the capsule polysaccharide ofC. jejuniand the MeOPN modification modulate the host immune response.

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The Bacterial Second Messenger Cyclic di-GMP Regulates Brucella Pathogenesis and Leads to Altered Host Immune Response

Infection and Immunity ◽

10.1128/iai.00531-16 ◽

2016 ◽

Vol 84 (12) ◽

pp. 3458-3470 ◽

Cited By ~ 11

Author(s):

Mike Khan ◽

Jerome S. Harms ◽

Fernanda M. Marim ◽

Leah Armon ◽

Cherisse L. Hall ◽

...

Keyword(s):

Immune Response ◽

Second Messenger ◽

Host Immune Response ◽

Vital Role ◽

Host Cells ◽

Content Type ◽

Type Iv

Brucella species are facultative intracellular bacteria that cause brucellosis, a chronic debilitating disease significantly impacting global health and prosperity. Much remains to be learned about how Brucella spp. succeed in sabotaging immune host cells and how Brucella spp. respond to environmental challenges. Multiple types of bacteria employ the prokaryotic second messenger cyclic di-GMP (c-di-GMP) to coordinate responses to shifting environments. To determine the role of c-di-GMP in Brucella physiology and in shaping host- Brucella interactions, we utilized c-di-GMP regulatory enzyme deletion mutants. Our results show that a Δ bpdA phosphodiesterase mutant producing excess c-di-GMP displays marked attenuation in vitro and in vivo during later infections. Although c-di-GMP is known to stimulate the innate sensor STING, surprisingly, the Δ bpdA mutant induced a weaker host immune response than did wild-type Brucella or the low-c-di-GMP guanylate cyclase Δ cgsB mutant. Proteomics analysis revealed that c-di-GMP regulates several processes critical for virulence, including cell wall and biofilm formation, nutrient acquisition, and the type IV secretion system. Finally, Δ bpdA mutants exhibited altered morphology and were hypersensitive to nutrient-limiting conditions. In summary, our results indicate a vital role for c-di-GMP in allowing Brucella to successfully navigate stressful and shifting environments to establish intracellular infection.

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Characterization of Host and Microbial Determinants in Individuals with Latent Tuberculosis Infection Using a Human Granuloma Model

mBio ◽

10.1128/mbio.02537-14 ◽

2015 ◽

Vol 6 (1) ◽

Cited By ~ 66

Author(s):

Evelyn Guirado ◽

Uchenna Mbawuike ◽

Tracy L. Keiser ◽

Jesus Arcos ◽

Abul K. Azad ◽

...

Keyword(s):

Immune Response ◽

Mycobacterium Tuberculosis ◽

Immune Status ◽

Host Immune Response ◽

Granuloma Formation ◽

Content Type ◽

Transcriptional Signature ◽

Latent Tb ◽

Latent Tb Infection

ABSTRACTGranulomas sit at the center of tuberculosis (TB) immunopathogenesis. Progress in biomarkers and treatment specific to the human granuloma environment is hindered by the lack of a relevant and tractable infection model that better accounts for the complexity of the host immune response as well as pathogen counterresponses that subvert host immunity in granulomas. Here we developed and characterized anin vitrogranuloma model derived from human peripheral blood mononuclear cells (PBMCs) and autologous serum. Importantly, we interrogated this model for its ability to discriminate between host and bacterial determinants in individuals with and without latent TB infection (LTBI). By the use of this model, we provide the first evidence that granuloma formation, bacterial survival, lymphocyte proliferation, pro- and anti-inflammatory cytokines, and lipid body accumulation are significantly altered in LTBI individuals. Moreover, we show a specific transcriptional signature ofMycobacterium tuberculosisassociated with survival within human granuloma structures depending on the host immune status. Our report provides fundamentally new information on how the human host immune status and bacterial transcriptional signature may dictate early granuloma formation and outcome and provides evidence for the validity of the granuloma model and its potential applications.IMPORTANCEIn 2012, approximately 1.3 million people died from tuberculosis (TB), the highest rate for any single bacterial pathogen. The long-term control of TB requires a better understanding ofMycobacterium tuberculosispathogenesis in appropriate research models. Granulomas represent the characteristic host tissue response to TB, controlling the bacilli while concentrating the immune response to a limited area. However, complete eradication of bacteria does not occur, sinceM. tuberculosishas its own strategies to adapt and persist. Thus, theM. tuberculosis-containing granuloma represents a unique environment for dictating both the host immune response and the bacterial response. Here we developed and characterized anin vitrogranuloma model derived from blood cells of individuals with latent TB infection that more accurately defines the human immune response and metabolic profiles ofM. tuberculosiswithin this uniquely regulated immune environment. This model may also prove beneficial for understanding other granulomatous diseases.

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