Publikationsdatenbank

Differential immunomodulation in human monocytes versus macrophages by filarial cystatin (2017)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Venugopal, Gopinath (WE 6)

Mueller, Marion (WE 6)

Hartmann, Susanne (WE 6)

Steinfelder, Svenja (WE 6)

Quelle

PLOS ONE

Bandzählung: 12

Heftzählung: 11

Seiten: e0188138

ISSN: 1932-6203

Sprache

Englisch

Verweise

DOI: 10.1371/journal.pone.0188138

Pubmed: 29141050

Kontakt

Institut für Immunologie

Robert-von-Ostertag-Str. 7-13
Gebäude 35
14163 Berlin
+49 30 838 51834

Abstract / Zusammenfassung

Parasitic nematodes have evolved powerful immunomodulatory molecules to enable their survival in immunocompetent hosts by subverting immune responses and minimizing pathological processes. One filarial molecule known to counteract host immune responses by inducing IL-10 and regulatory macrophages in mice is filarial cystatin. During a patent filarial infection monocytes encounter microfilariae in the blood, an event that occurs in asymptomatically infected filariasis patients that are immunologically hyporeactive. The microfilarial larval stage was formerly shown to induce human regulatory monocytes and macrophages. Thus, here we aim was to determine how filarial cystatin of the human pathogenic filaria Brugia malayi (BmCPI-2) contributes to immune hyporesponsiveness in human monocytes and macrophages elicited by microfilaria. For this purpose, filarial cystatin was depleted from microfilarial lysate (Mf). Detecting the immunomodulatory potential of cystatin-depleted Mf revealed that IL-10, but not IL-8 and IL-6 induction in monocytes and macrophages is dependent on the presence of cystatin. In addition, the Mf-induced expression of the regulatory surface markers PD-L1 and PD-L2 in human monocytes, but not in macrophages, is dependent on cystatin. While Mf-treated monocytes result in decreased CD4+ T-cell proliferation in a co-culture assay, stimulation of T-cells with human monocytes treated with cystatin-depleted Mf lead to a restoration of CD4+ T-cell proliferation. Moreover, IL-10 induction by cystatin within Mf was dependent on p38 and ERK in macrophages, but independent of the ERK pathway in monocytes. These findings indicate that filarial nematodes differentially trigger and exploit various signaling pathways to induce immunomodulation in different myeloid cell subsets.