Trained Immunity as a Prospective Tool against Emerging Respiratory Pathogens

Joseph, John

doi:10.3390/vaccines10111932

Cited by 3 publications

(2 citation statements)

References 68 publications

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“…These observations also support the idea that severe illness does not usually ensue if the host does not mount a nonspecific and overly aggressive inflammatory response ( Figure 1 and Figure 2 ). Thus, it is likely that vaccination initially acts as a sensitizer to the immune system, which is naïve to SARS-CoV-2, but that through this sensitization, when an actual infection happens later, the result is a more tolerant, subdued, and conditioned inflammatory response that does not overwhelm the host [ 148 , 149 , 150 ] ( Figure 2 ). Immune system desensitization is the process of gradually exposing an individual to an antigen so that their immune system becomes nonreactive [ 151 ].…”

Section: Calming the Inflammatory Storm By Conditioning The Immune Sy...mentioning

confidence: 99%

Protection against Severe Illness versus Immunity—Redefining Vaccine Effectiveness in the Aftermath of COVID-19

Roche,

Odeh,

Andar

et al. 2023

Microorganisms

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Anti-SARS-CoV-2 vaccines have played a pivotal role in reducing the risk of developing severe illness from COVID-19, thus helping end the COVID-19 global public health emergency after more than three years. Intriguingly, as SARS-CoV-2 variants emerged, individuals who were fully vaccinated did get infected in high numbers, and viral loads in vaccinated individuals were as high as those in the unvaccinated. However, even with high viral loads, vaccinated individuals were significantly less likely to develop severe illness; this begs the question as to whether the main effect of anti-SARS-CoV-2 vaccines is to confer protection against severe illness or immunity against infection. The answer to this question is consequential, not only to the understanding of how anti-SARS-CoV-2 vaccines work, but also to public health efforts against existing and novel pathogens. In this review, we argue that immune system sensitization-desensitization rather than sterilizing immunity may explain vaccine-mediated protection against severe COVID-19 illness even when the SARS-CoV-2 viral load is high. Through the lessons learned from COVID-19, we make the case that in the disease’s aftermath, public health agencies must revisit healthcare policies, including redefining the term “vaccine effectiveness.”

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Section: Calming the Inflammatory Storm By Conditioning The Immune Sy...mentioning

confidence: 99%

Protection against Severe Illness versus Immunity—Redefining Vaccine Effectiveness in the Aftermath of COVID-19

Roche,

Odeh,

Andar

et al. 2023

Microorganisms

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“…It was originally assumed to stimulate bovine TLR-9, as described for CpG motifs in humans and mice ( 27 – 29 ), but more recent work concluded the downstream effects were mediated by the STING/cGAS pathway ( 30 ). Ultimately, both paramunity (to aid vaccination against an unrelated pathogen) and the use of CpG motifs directly relate to the relatively recently defined concept of trained immunity ( 31 , 32 ).…”

Section: Introductionmentioning

confidence: 99%

Immunostimulation of Asian elephant (Elephas maximus) blood cells by parapoxvirus ovis and CpG motif-containing bacterial plasmid DNA upregulates innate immune gene expression

Haycock,

Maehr,

Dastjerdi

et al. 2024

Front. Immunol.

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The immune system of Asian elephants (Elephas maximus) is poorly studied, compared to that of livestock, rodents or humans. The innate immune response has become a focus of interest in relation to Elephant endotheliotropic herpesviruses (EEHVs). EEHVs cause a fatal hemorrhagic disease (EEHV-HD) and are a significant threat to captive Asian elephant populations worldwide. Similar to other herpesvirus infections, nearly all animals become infected, but only some develop disease. As progression to EEHV-HD is often acute, a robust innate immune response is crucial to control EEHV infections. This is invariably true of the host in the first instance, but it can also potentially be modulated by intervention strategies. Here, two immunostimulant veterinary medicinal products, authorized for use in domestic species, were tested for their ability to induce innate anti-viral immune responses in Asian elephant blood cells. Sequence data were obtained for a range of previously unidentified Asian elephant immune genes, including C-X-C motif chemokine ligand 10 (CXCL10), interferon stimulated gene 15 (ISG15) and myxovirus GTPase 1 (Mx1), and were employed in the design of species-specific qPCR assays. These assays were subsequently used in analyses to determine fold changes in gene expression over a period of 24 hours. This study demonstrates that both immunostimulant medications are capable of inducing significant innate anti-viral immune responses which suggests that both could be beneficial in controlling EEHV infections in Asian elephants.

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The innate memory response of macrophages to Mycobacterium tuberculosis is shaped by the nature of the antigenic stimuli

Kumar,

Kolloli,

Singh

et al. 2024

Microbiol Spectr

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Innate immune cells, such as macrophages, mount an immune response upon exposure to antigens and pathogens. Emerging evidence shows that macrophages exposed to an antigen can generate a “memory-like” response (a.k.a. trained immunity), which confers a non-specific and enhanced response upon subsequent stimulation with a second antigen/microbe. This trained immunity has been implicated in the enhanced response of macrophages against several invading pathogens. However, the association between the nature of the antigen and the corresponding immune correlate of elicited trained immunity is not fully understood. Similarly, the response of macrophages trained and restimulated with homologous stimulants to subsequent infection by pathogenic Mycobacterium tuberculosis (Mtb) remains unexplored. Here, we report the immune and metabolic profiles of trained immunity in human THP-1-derived macrophages after homologous training and restimulation with BCG, LPS, purified protein Derivative (PPD), heat-killed Mtb strains HN878 (hk-HN), and CDC1551 (hk-CDC). Furthermore, the impact of training on the autophagic and antimicrobial responses of macrophages with or without subsequent infection by clinical Mtb isolates HN878 and CDC1551 was evaluated. Results show that repeated stimulation of macrophages with different antigens displays distinct pro-inflammatory, metabolic, antimicrobial, and autophagy induction profiles. These macrophages also induce a differential antimicrobial response upon infection with clinical Mtb HN878 and CDC1551 isolates. A significantly reduced intracellular bacterial load was noted in the stimulated macrophages, which was augmented by the addition of rapamycin, an autophagy inducer. These observations suggest that the nature of the antigen and the mode of stimulation shape the magnitude and breadth of macrophage innate memory response, which impacts subsequent response to Mtb infection. IMPORTANCE Trained immunity (a.k.a. innate memory response) is a novel concept that has been rapidly emerging as a mechanism underpinning the non-specific immunity of innate immune cells, such as macrophages. However, the association between the nature of the stimuli and the corresponding immune correlate of trained immunity is not fully understood. Similarly, the kinetics of immunological and metabolic characteristics of macrophages upon “training” by the same antigen as primary and secondary stimuli (homologous stimulation) are not fully characterized. Furthermore, the ability of antigens such as purified protein derivative (PPD) and heat-killed-Mtb to induce trained immunity remains unknown. Similarly, the response of macrophages primed and trained by homologous stimulants to subsequent infection by pathogenic Mtb is yet to be reported. In this study, we evaluated the hypothesis that the nature of the stimuli impacts the depth and breadth of trained immunity in macrophages, which differentially affects their response to Mtb infection.

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Trained Immunity as a Prospective Tool against Emerging Respiratory Pathogens

Cited by 3 publications

References 68 publications

Protection against Severe Illness versus Immunity—Redefining Vaccine Effectiveness in the Aftermath of COVID-19

Protection against Severe Illness versus Immunity—Redefining Vaccine Effectiveness in the Aftermath of COVID-19

Immunostimulation of Asian elephant (Elephas maximus) blood cells by parapoxvirus ovis and CpG motif-containing bacterial plasmid DNA upregulates innate immune gene expression

The innate memory response of macrophages to Mycobacterium tuberculosis is shaped by the nature of the antigenic stimuli

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