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Microbes & Immunity RANTES/CCL5 and ezrin peptide RepG3 for long COVID

name “yellow fever.” RANTES/CCL5 is also important responses supported by T-cell help. Th1 CD4 T-cells
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for defense against tick-borne encephalitis. induced by RANTES/CCL5, which express interferon-
gamma (INF-γ), IL-2, and TNF-α, support CD8 CTL to
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3.12. RANTES/CCL5 and bacterial infections attack fungus-infected cells and control candidiasis. In
The prevalence of Chlamydia trachomatis has increased contrast, a dominance of IL-4 expressing Th2 CD4 T-cells
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50-fold in 40 years in the USA, becoming the most common is associated with more persistent candidiasis. 47
sexually transmitted infection. Following genital chlamydial
infection, RANTES/CCL5 amplifies mucosal immunity, 3.14. RANTES/CCL5 and Trichomonas vaginalis (TV)
mediating an early T helper Type 1 (Th1)-associated (protozoan) infections
immune response. The activation and recruitment of RANTES/CCL5 adaptive immune amplification is
specific Th1 T-cells that activate CD8 CTL, which support important for defense against a wide spectrum of
+
B-cells to manufacture IgG2a subclass antibodies as well parasitic diseases. The extracellular protozoan parasite
as IgA responses against Chlamydia, subsequently leads TV is one of the most common sexually transmitted
to the clearance of Chlamydia. RANTES/CCL5 and a pathogens, infecting over 200 million men and women
functional CCR5 receptor are crucial for this protective each year. In more than half of those diagnosed, TV
anti-chlamydial immunity. In addition, RANTES/CCL5 infection is asymptomatic but recurrent. When resident
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amplifies systemic adaptive immunity against a spectrum in the urogenital tract over a long period of time, TV is
of bacterial infections, including Streptococcus pneumoniae responsible for infertility, preterm birth, low birth weight,
and Mycobacterium tuberculosis. 44,45 and bacterial vaginosis with chronic infection of the upper
reproductive tract endocervical epithelial cells.
3.13. RANTES/CCL5 and Candida fungal infections
TV persists because it suppresses both the early innate
RANTES/CCL5 is critical for effective adaptive antifungal immunity mediated by NF-κB expression of IL-8 and later
defense. In HIV-infected AIDS patients with depleted adaptive immunity CD4 T-cell help, CD8 CTL, and B-cell
+
+
CD4 T-cells, the importance of RANTES/CCL5 in responses mediated by RANTES/CCL5 expression. TV
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supporting CD4 T-cell helps of CD8 CTL to provide achieves this effective suppression of immune-responses
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effective immunity against Candida albicans is obvious: to its infection by carrying its own intra-protozoan
The loss of CD4 T-cell help correlates with the prevalence symbiotic double-stranded RNA virus, called TV-virus
+
of oral-pharyngeal candidiasis in these patients. (TVV), which expresses immune-suppressive proteins that
Mucosal fungal infection of the vagina and oral cavity inhibit RANTES/CCL5 and proinflammatory cytokine
by C. albicans is one of the most common fungal infections. expression. In contrast, TV, which is free from symbiotic
Three-quarters of all women had at least one episode of TVV infection, cannot inhibit RANTES/CCL5, NF-κB, or
mucosal inflammation, itching, and vaginal discharges IL-8 expression and cannot survive in uterine endocervical
caused by overgrowth of C. albicans. Although 50% of cells under effective immune surveillance. 48
people carry this organism and low levels of C. albicans 4. RANTES/CCL5 modulation of immune
form part of the normal oral and vaginal microflora, chronic
recurrent overgrowth of C. albicans leading to candidiasis function
occurs in at least 10% of all sexually active women. 4.1. Binding of RANTES/CCL5 to CCR5 receptors
Peripheral blood mononuclear cells (PBMCs) triggers JAK/STAT signaling
respond to C. albicans infection with a rapid increase in RANTES/CCL5 binds to CCR5 receptors exposed on the
RANTES/CCL5 expression and secretion. RANTES/ surface of many cell types, including T-cells, monocytes,
CCL5 chemoattracts activated Th1 T-cells, dendritic cells, macrophages, dendritic cells, eosinophils, and basophils.
and monocytes expressing CCR5 receptors and support CCR5 has a looped architecture with seven transmembrane
aggressive CD8 CTL responses to fungus-infected domains that stitch the receptor to the phospholipid
+
tissues. The capacity of the immune system to respond membrane. In T-cells, the binding of RANTES/CCL5 to
to C. albicans infection with efficient RANTES/CCL5 CCR5 receptors is associated with the amplification of a
expression is an important factor in the induction of an dominant Th-1 immune response. At physiological serum
effective T-cell-mediated anti-fungal response that stops concentrations, RANTES/CCL5 binds with high affinity to
chronic candidiasis. 46 CCR5 receptors on the cell surface of T-cells but also to
However, the immunological defense against C. albicans CCR1, CCR3, and CCR4. 49
is complex and is dependent on the cross-regulation of On docking of extracellular RANTES/CCL5 to CCR5
early innate immune responses and later adaptive immune receptors on the cell surface, an allosteric shape-change

Volume 1 Issue 1 (2024) 7 doi: 10.36922/mi.2474