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Peculiarities of innate immune memory in crustaceans

Low CF, Chong CM

Fish Shellfish Immunol, 2020 Sep;104:605-612.
PMID: 32619624 DOI: 10.1016/j.fsi.2020.06.047

Classical characteristic of the innate immune system is the lack of ability to build up immunological memory, contrast to the adaptive immune system that is capable of "remembering" antigens, and rapidly mount a greater magnitude of immune response upon subsequent exposure to the same antigens. Peculiarly, immunological memory of innate immunity is evidenced in invertebrates. At least three different memory phenomena have been described, namely sustained unique response, recalled response, and immune shift. Studies attended to decipher the mechanistic biology of the innate immune memory reveals the role of epigenetics, which modulates the response of immune memory, and the heritability of immune memory to subsequent generations. A parthenogenetic Artemia model demonstrated successful transgenerational epigenetic inheritance of resistance trait against Vibrio campbellii. Following, the role of invertebrate hemocytes and Down syndrome cell adhesion molecule (Dscam) in innate immune memory is reviewed. While there is no vertebrate antibody homolog found in invertebrates, Dscam was found to resemble the functionality of vertebrate antibody. Insight of Dscam as immune factor was illustrated further in the current review.

Matched MeSH terms: Immunologic Memory*
Fulltext Reduced CD4+ terminally differentiated effector memory T cells in moderate-severe house dust mites sensitized allergic rhinitis patients

Sani MM, Ashari NSM, Abdullah B, Wong KK, Musa KI, Mohamud R, et al.

Asian Pac J Allergy Immunol, 2019 Sep;37(3):138-146.
PMID: 29981564 DOI: 10.12932/AP-191217-0220

BACKGROUND: Terminally differentiated effector memory (TEMRA) T cells exert potent effector function after activation. The proportions of CD4+ T cell subsets especially memory cells in allergic rhinitis (AR) patients sensitized to house dust mites (HDMs) have not been extensively studied.
OBJECTIVE: This study aimed to compare the mean percentages and absolute counts of CD4+ memory T cell subsets between: (i) non-allergic controls and AR patients; (ii) mild AR patients and moderate-severe AR patients.
METHODS: Sensitization to Dermatophagoides farinae and Dermatophagoides pteronyssinus were determined in 33 non -allergic controls, 28 mild AR and 29 moderate-severe AR patients. Flow cytometry was used to determine the percentage of CD4+ na?ve (TN; CD45RA+CCR7+), central memory (TCM; CD45RA-CCR7+), effector memory (TEM; CD45RA-CCR7-) and TEMRA (CD45RA+CCR7-) T cells from the peripheral blood. The absolute counts of CD4+ T cell subsets were obtained by dual platform method from flow cytometer and hematology analyzer.
RESULTS: There were no significant differences in the mean percentages and absolute counts of CD4+ T cell subsets between non-allergic controls and AR patients sensitized to HDMs. However, there were significant reduction in the mean percentage (p=0.0307) and absolute count (p=0.0309) of CD4+ TEMRA cells in moderate-severe AR patients compared to mild AR patients sensitized to HDMs and 13/24 (54.2%) moderate-severe AR patients sensitized to HDMs had persistent symptoms.
CONCLUSION: Reduction in the mean percentage and absolute count of CD4+CD45RA+CCR7- TEMRA cells were observed in moderate-severe AR patients compared to mild AR patients in our population of AR patients sensitized to HDMs.

Matched MeSH terms: Immunologic Memory*
Immune responses against enterovirus A71 infection: Implications for vaccine success

Aw-Yong KL, NikNadia NMN, Tan CW, Sam IC, Chan YF

Rev Med Virol, 2019 09;29(5):e2073.
PMID: 31369184 DOI: 10.1002/rmv.2073

Enterovirus A71 (EV-A71) from the Picornaviridae family is an important emerging pathogen causing hand, foot, and mouth disease (HFMD) outbreaks worldwide. EV-A71 also caused fatal neurological complications in young children especially in Asia. On the basis of seroepidemiological studies from many Asian countries, EV-A71 infection is very common. Children of very young age are particularly vulnerable. Large-scale epidemics that occur every 3 to 4 years are associated with accumulation of an immunologically naive younger population. Capsid proteins especially VP1 with the presence of major B- and T-cell epitopes are the most antigenic proteins. The nonstructural proteins mainly contribute to T-cell epitopes that induce cross-reactive immune responses against other enteroviruses. Dominant epitopes and their neutralization magnitudes differ in mice, rabbits, and humans. Neutralizing antibody is sufficient for immune protection, but poorer cellular immunity may lead to severe neurological complications and deaths. Some chemokines/cytokines are consistently found in severely ill patients, for example, IL-6, IL-10, IL-17A, MCP-1, IL-8, MIG, IP-10, IFN-γ, and G-CSF. An increase in white cell counts is a risk factor for severe HFMD. Recent clinical trials on EV-A71 inactivated vaccine showed >90% efficacy and a robust neutralization response that was protective, indicating neutralizing antibody correlates for protection. No protection against other enteroviruses was observed. A comprehensive understanding of the immune responses to EV-A71 infection will benefit the development of diagnostic tools, potential therapeutics, and subunit vaccine candidates. Future development of a multivalent enterovirus vaccine will require knowledge of correlates of protection, understanding of cross-protection and memory T-cell responses among enteroviruses.

Matched MeSH terms: Immunologic Memory
Enhancement of immune response against Mycobacterium tuberculosis HspX antigen by incorporation of combined molecular adjuvant (CASAC)

Lew MH, Norazmi MN, Tye GJ

Mol Immunol, 2020 Jan;117:54-64.
PMID: 31739193 DOI: 10.1016/j.molimm.2019.10.023

Tuberculosis (TB) is one of the deadliest human diseases worldwide caused by mycobacterial infection in the lung. Bacillus Calmette-Guerin (BCG) vaccine protects against disseminated TB in children, but its effectiveness is still questionable due to highly variable protections in adolescence and elderly individuals. Targeting the latency M.tb antigen is a recent therapeutic approach to eradicate dormant pathogen that could possibly lead to disease activation. In this study, we aimed to potentiate immune responses elicited against 16 kDa α-crystalline (HspX) tuberculosis latency antigen by incorporation of Combined Adjuvant for Synergistic Activation of Cellular immunity (CASAC). Histidine-tagged recombinant HspX protein was initially produced in Escherichia coli and purified using Ni-NTA chromatography. To evaluate its adjuvanticity, C57BL/6 mice (n = 5) were initially primed and intradermally immunised in 2-weeks interval for 4 rounds with recombinant HspX, formulated with and without CASAC. Humoral and cell-mediated immune responses elicited against HspX antigen were evaluated using ELISA and Flow Cytometry. Our findings showed that CASAC improved humoral immunity with increased antigen-specific IgG1 and IgG2a antibody response. Stronger CD8+ and Th1-driven immunity was induced by CASAC formulation as supported by elevated level of IFN-γ, TNF-α, IL-12 and IL-17A; and with low IL-10 secretion. Interestingly, adjuvanted HspX vaccine triggered a higher percentage of effector memory T-cell population than those immunised with unadjuvanted vaccine. In conclusion, CASAC adjuvant has great potential to enhance immunogenicity elicited against HspX antigen, which could be an alternative regimen to improve the efficacy of future therapeutic vaccine against Mycobacterium tuberculosis.

Matched MeSH terms: Immunologic Memory
Fulltext Protection against henipaviruses in swine requires both, cell-mediated and humoral immune response

Pickering BS, Hardham JM, Smith G, Weingartl ET, Dominowski PJ, Foss DL, et al.

Vaccine, 2016 09 14;34(40):4777-86.
PMID: 27544586 DOI: 10.1016/j.vaccine.2016.08.028

Hendra virus (HeV) and Nipah virus (NiV) are members of the genus Henipavirus, within the family Paramyxoviridae. Nipah virus has caused outbreaks of human disease in Bangladesh, Malaysia, Singapore, India and Philippines, in addition to a large outbreak in swine in Malaysia in 1998/1999. Recently, NiV was suspected to be a causative agent of an outbreak in horses in 2014 in the Philippines, while HeV has caused multiple human and equine outbreaks in Australia since 1994. A swine vaccine able to prevent shedding of infectious virus is of veterinary and human health importance, and correlates of protection against henipavirus infection in swine need to be better understood. In the present study, three groups of animals were employed. Pigs vaccinated with adjuvanted recombinant soluble HeV G protein (sGHEV) and challenged with HeV, developed antibody levels considered to be protective prior to the challenge (titers of 320). However, activation of the cell-mediated immune response was not detected, and the animals were only partially protected against challenge with 5×10(5) PFU of HeV per animal. In the second group, cross-neutralizing antibody levels against NiV in the sGHEV vaccinated animals did not reach protective levels, and with no activation of cellular immune memory, these animals were not protected against NiV. Only pigs orally infected with 5×10(4) PFU of NiV per animal were protected against nasal challenge with 5×10(5) PFU of NiV per animal. This group of pigs developed protective antibody levels, as well as cell-mediated immune memory. Peripheral blood mononuclear cells restimulated with UV-inactivated NiV upregulated IFN-gamma, IL-10 and the CD25 activation marker on CD4(+)CD8(+) T memory helper cells and to lesser extent on CD4(-)CD8(+) T cells. In conclusion, both humoral and cellular immune responses were required for protection of swine against henipaviruses.

Matched MeSH terms: Immunologic Memory
Fulltext Immunological history governs human stem cell memory CD4 heterogeneity via the Wnt signaling pathway

Kared H, Tan SW, Lau MC, Chevrier M, Tan C, How W, et al.

Nat Commun, 2020 02 10;11(1):821.
PMID: 32041953 DOI: 10.1038/s41467-020-14442-6

The diversity of the naïve T cell repertoire drives the replenishment potential and capacity of memory T cells to respond to immune challenges. Attrition of the immune system is associated with an increased prevalence of pathologies in aged individuals, but whether stem cell memory T lymphocytes (TSCM) contribute to such attrition is still unclear. Using single cells RNA sequencing and high-dimensional flow cytometry, we demonstrate that TSCM heterogeneity results from differential engagement of Wnt signaling. In humans, aging is associated with the coupled loss of Wnt/β-catenin signature in CD4 TSCM and systemic increase in the levels of Dickkopf-related protein 1, a natural inhibitor of the Wnt/β-catenin pathway. Functional assays support recent thymic emigrants as the precursors of CD4 TSCM. Our data thus hint that reversing TSCM defects by metabolic targeting of the Wnt/β-catenin pathway may be a viable approach to restore and preserve immune homeostasis in the context of immunological history.

Matched MeSH terms: Immunologic Memory
Fulltext The modulation of PPARγ1 and PPARγ2 mRNA expression by ciglitazone in CD3/CD28-activated naïve and memory CD4+ T cells

Norazmi MN, Mohamed R, Nurul AA, Yaacob NS

Clin. Dev. Immunol., 2012;2012:849195.
PMID: 22548115 DOI: 10.1155/2012/849195

Given their roles in immune regulation, the expression of the nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ) 1 and 2 isoforms was investigated in human naïve (CD45RA+) and memory (CD45RO+) CD4+ T cells. Stimulation of both types of cells via the CD3/CD28 pathway resulted in high expression of both PPARγ receptors as measured by real-time PCR. Treatment with the PPARγ agonist, ciglitazone, increased PPARγ1 expression but decreased PPARγ2 expression in stimulated naïve and memory cells. Furthermore, when present, the magnitude of both PPARγ receptors expression was lower in naïve cells, perhaps suggesting a lower regulatory control of these cells. Similar profiles of selected proinflammatory cytokines were expressed by the two cell types following stimulation. The induction of PPARγ1 and suppression of PPARγ2 expressions in naïve and memory CD4+ T cells in the presence of ciglitazone suggest that the PPARγ subtypes may have different roles in the regulation of T-cell function.

Matched MeSH terms: Immunologic Memory
Fulltext Changing survival, memory cell compartment, and T-helper balance of lymphocytes between severe and mild asthma

Abdulamir AS, Hafidh RR, Abubakar F, Abbas KA

BMC Immunol, 2008;9:73.
PMID: 19087256 DOI: 10.1186/1471-2172-9-73

BACKGROUND: Asthma is a complicated network of inflammatory reactions. It is classified into mild, moderate, and severe persistent asthma. The success of asthma therapy relies much on understanding the underlying mechanisms of inflammation at each stage of asthma severity. The aim of this study was to explore the differences in apoptotic potential, CD4/CD8 ratio, memory compartment, and T- helper (Th) 1 and 2 profile of peripheral blood lymphocytes (PBL) in patients with mild intermittent asthma and severe persistent asthma during exacerbation periods.
RESULTS: Four research lines were investigated and compared among mild asthmatics, severe asthmatics, and healthy groups by applying immunocytochemical staining of PBL. Antiapoptotic and proapoptotic proteins with Bcl-2/Bax ratio, CD4, CD8 markers with CD4+/CD8+ ratio, CD45RO+, CD45RA+ markers with memory/naive ratio (CD45RO+/CD45RA+). Th2/Th1 cytokines balance represented by IL-4/IFN-gamma ratio was measured by enzyme-linked immunosorbent assay (ELISA) for in vitro PBL cytokine synthesis. It was found that Bcl-2/Bax ratio was higher in severe than in mild asthmatics which in turn was higher than in healthy group. And memory/naive ratio of PBL was higher in severe than in mild asthmatics. Moreover, memory cells, CD45RO+ and CD45RO+/CD45RA+ ratio were correlated directly with Bcl-2/Bax, in severe and mild asthma patients. In contrast, CD4+/CD8+ ratio was not changed significantly among healthy group, mild and severe asthmatics. However, CD8+ cells were correlated directly with memory cells, CD45RO+, in severe asthmatics only. Interestingly, the dominant profile of cytokines appeared to change from T helper 2 (Th2) in mild asthmatics to T helper 1 (Th1) in severe asthmatics where the lowest in vitro IL-4/IFN-gamma ratio and highest IFN-gamma were found.
CONCLUSION: It was concluded that the underlying mechanisms of inflammation might vary greatly with asthma stage of severity. Mild intermittent asthma is mainly Th2 allergen-oriented reaction during exacerbations with good level of apoptosis making the inflammation as self-limiting, while in severe persistent asthma, the inflammatory reaction mediated mainly by Th1 cytokines with progressive loss of apoptosis leading to longer exacerbations, largely expanded memory cells, CD45RO+, leading to persistent baseline inflammation.

Matched MeSH terms: Immunologic Memory