Acute Penicillium marneffei infection stimulates host M1/M2a macrophages polarization in BALB/C mice

Abstract

Background Penicillium marneffei (P. marneffei) is a thermally dimorphic fungus pathogen that causes fatal infection. Alveolar macrophages are innate immune cells that have critical roles in protection against pulmonary fungal pathogens and the macrophage polarization state has the potential to be a deciding factor in disease progression or resolution. The aim of this study was to investigate mouse alveolar macrophage polarization states during P. marneffei infection.ResultsWe used enzyme-linked immunosorbent (ELISA) assays, quantitative real-time PCR (qRT-PCR), and Griess, arginase activity to evaluate the phenotypic markers of alveolar macrophages from BALB/C mice infected with P. marneffei. We then treated alveolar macrophages from infected mice with P. marneffei cytoplasmic yeast antigen (CYA) and investigated alveolar macrophage phenotypic markers in order to identify macrophage polarization in response to P. marneffei antigens. Our results showed: i) P. marneffei infection significantly enhanced the expression of classically activated macrophage (M1)-phenotypic markers (inducible nitric oxide synthase [iNOS] mRNA, nitric oxide [NO], interleukin-12 [IL-12], tumor necrosis factor-alpha [TNF-α]) and alternatively activated macrophage (M2a)-phenotypic markers (arginase1 [Arg1] mRNA, urea) during the second week post-infection. This significantly decreased during the fourth week post-infection. ii) During P. marneffei infection, CYA stimulation also significantly enhanced the expression of M1 and M2a-phenotypic markers, consistent with the results for P. marneffei infection and CYA stimulation preferentially induced M1 subtype.ConclusionsThe data from the current study demonstrated that alveolar macrophage M1/M2a subtypes were present in host defense against acute P. marneffei infection and that CYA could mimic P. marneffei to induce a host immune response with enhanced M1 subtype. This could be useful for investigating the enhancement of host anti-P. marneffei immune responses and to provide novel ideas for prevention of P. marneffei-infection.Electronic supplementary materialThe online version of this article (doi:10.1186/s12866-017-1086-3) contains supplementary material, which is available to authorized users.

<p>Dendritic Cells Promote Treg Expansion but Not Th17 Generation in Response to <em>Talaromyces marneffei</em> Yeast Cells</p>

“…41 Therefore, the dominance of Treg cells could be associated with the down-regulation of RORγt expression and the suppression of Th17 cells. On the basis of previous studies, 2,7,28 we predicted that increased inflammatory effector T cells (such as Th1 and Th17) and M1 macrophages activation in response to T. marneffei are beneficial for pathogen elimination. Given that Th17 is critical for host defense in fungal infections, [17][18][19]21,22 the immune cell pattern switching to a tolerogenic phenotype may be harmful for the defense against T. marneffei.…”

“…The T. marneffei strain (GXHCBR) used in our study was isolated from lung, liver, and spleen tissues of an infected bamboo rat in Hechi, Guangxi, China as described previously. 28 The strain was previously identified by gold-standard deoxyribonucleic acid sequencing of the fungal internal transcribed spacer region. 28 T. marneffei strain was plated in potato dextrose agar medium and incubated at 25°C for 10 days.…”

“…28 The strain was previously identified by gold-standard deoxyribonucleic acid sequencing of the fungal internal transcribed spacer region. 28 T. marneffei strain was plated in potato dextrose agar medium and incubated at 25°C for 10 days. Colonies were washed with sterile phosphatebuffered saline, and then yeast cells of T. marneffei were isolated by centrifugation.…”

Biochanin a Enhances the Defense Against Salmonella enterica Infection Through AMPK/ULK1/mTOR-Mediated Autophagy and Extracellular Traps and Reversing SPI-1-Dependent Macrophage (MΦ) M2 Polarization

“…The balance of M1/M2 MΦs determines the tissue inflammation and tissue damage (Dey et al, 2014 ). Different pathogen infections have different effects on the polarization of MΦs and most of them improve MΦs toward M1 phenotype (Khan et al, 2015 ; Dai et al, 2017 ; Farias et al, 2017 ; Hou et al, 2017 ). Salmonella has been proved to induce MΦ polarization toward M2 phenotype depending on SPI-1 (Kyrova et al, 2012 ), our results in vitro were similar to the previous reports.…”

Innate Immunity Acts as the Major Regulator in Talaromyces marneffei Coinfected AIDS Patients: Cytokine Profile Surveillance During Initial 6-Month Antifungal Therapy

“…During the immunoinflammatory reaction, the activated immunocytes produce pro- and anti-inflammatory cytokines, which simultaneously interact and form a complex inflammatory network, the dynamic balance of which influences the progression and outcome of the disease [7]. The intracellular infection of macrophages is characteristic of T. marneffei pathology, and recent studies reported that the activation of macrophage-derived cytokines (ie, TNF-α and IFN-γ) is elevated and responsible for T. marneffei clearance [8, 9]. However, these experiments were performed in vitro by stimulating macrophages with T. marneffei or in animal models.…”