Innate lymphoid cells in peripheral blood of patients with American Cutaneous Leishmaniasis

Abstract

Innate lymphoid cells (ILCs) are classified by the expression of specific transcription factors: ILC1 depending on T‐bet for IFN‐γ production; ILC2 depending on GATA3 for IL‐5 and IL‐13; and ILC3 depending on ROR‐γτ and AHR for IL‐17 and IL‐22. This study aimed to determine circulating ILCs in 23 patients with localized (LCL) = 7, mucocutaneous (MCL) = 10, intermediate (ICL) = 3 and diffuse (DCL) = 3 cutaneous leishmaniasis and 17 healthy controls from endemic area (EC) = 9 and non‐endemic area (HC) = 8. Results evidenced a higher proportion of ILC1 in LCL than controls and MCL. ILC2 was higher in DCL compared with controls. ILC3 s were abundant in MCL and DCL concerning controls. A prevalence ratio was calculated to approach cell plasticity: in LCL, the ratio showed a prevalence of ILC1/ILC3 (plasticity 1), in contrast to DCL, and controls, where ILC2/ILC3 (plasticity 3) is prevalent. Also, MCL and ICL showed higher ILC1/ILC2 (plasticity 2). These results suggest that ILC1 and ILC3 in LCL are associated with disease control and regulation of inflammation, while MCL and ICL are related to immunopathology and uncontrolled inflammation. In DCL, ILC2 is associated with the tolerogenic state of these patients.

Leishmaniasis: Immune Cells Crosstalk in Macrophage Polarization

“…For example, LCL (Localized Cutaneous Leishmaniasis) has a higher presence of both ILC1 and ILC3 responses. Therefore, it may be responsible for promoting a Th1 response, which can help control the infection [65]. Specifically, in LCL patients, a unique subtype of ILC1 that requires T-bet for differentiation can produce significant amounts of IFN-γ and TNF-α when exposed to cytokines from infected cells, resulting in a more robust Th1 response and consequent classical macrophage activation, as previously observed in inflammatory bowel disease (IBD) and infection-induced colitis [66,67].…”

“…A study by Rodríguez et al (2021) showed the variability of different proportions of ILC phenotypes in other forms of Leishmaniasis. For example, LCL (Localized Cutaneous Leishmaniasis) has a higher presence of both ILC1 and ILC3 responses.…”

“…This process is essential for the body's protective response against Leishmania infections. On the other hand, in patients with DCL (Diffuse Cutaneous Leishmaniasis), there is a higher incidence of ILC2 and ILC3, suggesting an inclination to M2 macrophage phenotype, which results in type 1 response impairment, as observed in patients presenting T cell anergy and disseminated disease [65].…”

Eosinophils, but Not Type 2 Innate Lymphoid Cells, Are the Predominant Source of Interleukin 4 during the Innate Phase of Leishmania major Infection

“…Rodriguez et al studied the distribution of ILC1, ILC2 and ILC3 in the peripheral blood of Venezuelan patients with localized (LCL; n = 7), intermediate type (ICL; n = 3) or diffuse cutaneous leishmaniasis (DCL; n = 3) or with mucocutaneous leishmaniasis (MCL; n = 10) as compared to healthy controls ( n = 17). Although the underlying parasite species was not reported and the number of analyzed patients was small, the authors obtained evidence that ILC1 were more frequent in LCL patients, whereas ILC2 were the predominant ILC type in DCL patients, who exhibit T cell anergy and disseminated disease [ 43 ]. Singh et al reported that IL-17A-producing ILC3 were enriched in the skin lesions of C57BL/6 mice at day 7 of infection with L. major .…”

Role of ILC2s in Solid Tumors: Facilitate or Inhibit?

“…In a parabiotic mice model of inhibiting commensal bacteria with antibiotics, resting ILC2s residing in intestinal lamina propria are activated by IL-33 or helminths into iILC2s, which migrate to various extraintestinal tissues through sphingosine 1-phosphate (S1P)-mediated chemotaxis to participate in anti-helminth defense and tissue repair (18). hILC2s were previously considered to be exclusively tissue-resident, but this couldn't explain the increased abundance of ILC2s and other ILC subsets in peripheral blood of American cutaneous leishmaniasis patients compared with healthy volunteers (19). The latest research shows that, CD45RO + ILC2s are derived from resting CD45RA + ILC2s in airway inflammation and are regarded as human equivalent of the iILC2 subset (20).…”