Nocardia brasiliensis Induces an Immunosuppressive Microenvironment That Favors Chronic Infection in BALB/c Mice

Abstract

<jats:title>ABSTRACT</jats:title><jats:p><jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">Nocardia brasiliensis</jats:named-content>is an intracellular microorganism and the most common etiologic agent of actinomycetoma in the Americas. Several intracellular pathogens induce an immunosuppressive microenvironment through increases in CD4<jats:sup>+</jats:sup>Foxp3<jats:sup>+</jats:sup>regulatory T cells (Treg), thus downregulating other T-cell subpopulations and assuring survival in the host. In this study, we determined whether<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">N. brasiliensis</jats:named-content>modulates T-lymphocyte responses and their related cytokine profiles in a murine experimental model. We also examined the relationship between<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">N. brasiliensis</jats:named-content>immunomodulation and pathogenesis and bacterial survival. In early infection, Th17/Tc17 cells were increased at day 3 (<jats:italic>P</jats:italic>&lt; 0.05) in footpad tissue and spleen. Treg subpopulations peaked at days 7 and 15 (<jats:italic>P</jats:italic>&lt; 0.01) in the footpad and spleen, respectively. Transforming growth factor β1 (TGF-β1) and interleuki-10 (IL-10) are cytokines known for their immunosuppressive effects. During early and chronic infections, these cytokines were elevated with increased TGF-β1 levels from days 3 to 30 (<jats:italic>P</jats:italic>&lt; 0.01) and sustained IL-10 expression throughout infection compared to uninfected mice. IL-6 production was increased at day 3 (<jats:italic>P</jats:italic>&lt; 0.01), whereas gamma interferon (IFN-γ), IL-17A, and IL-23 levels were highest at day 15 postinfection (<jats:italic>P</jats:italic>&lt; 0.01) when a decrease in the bacterial load (&gt;1 log) was also observed (<jats:italic>P</jats:italic>&lt; 0.05). After these changes, at 30 to 60 days postinfection, IFN-γ production was decreased, whereas the expression of anti-inflammatory cytokines and the bacterial load again increased (<jats:italic>P</jats:italic>&lt; 0.05). The increment in Treg cells and the related cytokine profile correlated with reduced inflammation at day 15 (<jats:italic>P</jats:italic>&lt; 0.05) in the footpad. We conclude that<jats:named-content xmlns:xlink="http://www.w3.org/1999/xlink" content-type="genus-species" xlink:type="simple">N. brasiliensis</jats:named-content>modulates the immune system to induce an immunosuppressive microenvironment that benefits its survival during the chronic stage of infection.</jats:p>

Immunomodulatory effect of diethylcarbamazine in mice infected with Nocardia brasiliensis

“…In the case of lymphoproliferative index induced by ConA, lymphocyte responses from uninfected-untreated individuals (G-I) showed a pattern of continuous increase compared to all other groups until day 28. All infected group showed an apparently low proliferation of cells in the early days as has been described in the BALB/c mycetoma model [22]. The behavior of proliferation of the infected-untreated persons (G-II) was different and opposite from that of DEC-treated group (Fig.…”

Retnla down-regulation and IL-13-rich environment correlate with inflammation severity in experimental actinomycetoma byNocardia brasiliensis

“…The local presence of interleukin (IL)-12 and interferongamma (IFN-c) (Solis-Soto et al, 2008;Rosas-Taraco et al, 2012) indicates the activation of a Th1 cellular immune response. The humoral immune response is also activated, in which, apart from IgG antibodies, relatively high sustained levels of IgM antibodies seem important for partial protection in a complement-independent way (Salinas-Carmona & Perez-Rivera, 2004;Gonzalez-Suarez et al, 2009).…”

Meningitis and Ventriculitis due to <i>Nocardia araoensis</i> Infection

“…Given these low CD4 cell counts, we performed HIV-PCR during the course and bone marrow at autopsy, but no positive findings were obtained. In a study with BALB/c mice, Rosas-Taraco et al reported that infection by N. brasiliensis induced an immunosuppressive microenvironment in the chronic stage ( 18 ). Alcohol consumption can cause low CD4 cell counts via low levels of interleukin 2 ( 19 ).…”