Antibiotics induce polarization of pleural macrophages to M2-like phenotype in patients with tuberculous pleuritis

Abstract

Pleural macrophages play critical roles in pathogenesis of tuberculous pleuritis, but very little is known about their response to anti-tuberculosis antibiotics treatment. Here, we examined whether and how pleural macrophages change in phenotype, transcription and function following antibiotics treatment in patients with tuberculous pleuritis. Results show pro-inflammatory cytokines were down-regulated significantly post antibiotic treatment in the pleural effusions and pleural macrophages up-regulated markers characteristic of M2 macrophages such as CD163 and CD206. Differential expression analysis of transcriptomes from four paired samples before and after treatment identified 230 treatment-specific responsive genes in pleural macrophages. Functional analysis identified interferon-related pathway to be the most responsive genes and further confirmed macrophage polarization to M2-like phenotype. We further demonstrate that expression of a significant fraction of responsive genes was modulated directly by antibiotics in pleural macrophages in vitro. Our results conclude that pleural macrophages polarize from M1-like to M2-like phenotype within a mean of 3.5 days post antibiotics treatment, which is dependent on both pleural cytokine environment and direct modulatory effects of antibiotics. The treatment-specific genes could be used to study the roles of pleural macrophages in the pathogenesis of tuberculous pleuritis and to monitor the response to antibiotics treatment.

Different macrophage polarization between drug-susceptible and multidrug-resistant pulmonary tuberculosis

“…We observed a higher M2 macrophage polarization rate in TB patients treated with anti-TB drug regimens including pyrazinamide or a combination of pyrazinamide, prothionamide and cycloserine. Consistently, a previous report suggested that pyrazinamide treatment influences the host immune response [15,16,29]. These observations suggest that anti-TB drugs modulate the host immune response.…”

“…Especially in the case of TB, long-term medication with anti-TB drugs is necessary for successful treatment, and therefore, the effects of drug-mediated immunomodulation may be large. Some antimicrobial agents have immunomodulatory properties in vitro [12,28], and some anti-TB drugs induce M2-like polarization of pleural macrophages in patients with pleuritic TB [16]. We observed a higher M2 macrophage polarization rate in TB patients treated with anti-TB drug regimens including pyrazinamide or a combination of pyrazinamide, prothionamide and cycloserine.…”

“…Pyrazinamide treatment can influence the host immune response by reducing pro-inflammatory cytokine production in Mtb infection [15]. First-line anti-TB treatment in patients with tuberculous pleuritis induced M2 polarization of pleural macrophages [16]. Moxifloxacin suppresses the production of pro-inflammatory cytokines [17].…”

Differences of Interleukin-18 and Interleukin-10 Levels in Rifampicin Resistant and Rifampicin Sensitive Pulmonary Tuberculosis Patients in Dr. Soetomo Hospital Surabaya

“…Activation of M1 macrophages through the TLR2 signal pathway can be benefi cial for the host to inhibit growth and the survival of M. tuberculosis. 16,17 Increased activation of M1 macrophages in newly infected RR pulmonary TB will produce pro-infl ammatory cytokines which play a role in the mechanism of eliminating M. tuberculosis. This causes the level of pro-infl ammatory cytokines to be higher in RR pulmonary TB serum compared to RS pulmonary TB.…”

“…Initially, IL-10 is known to be secreted by antigen-stimulated Th2, but it is now known that IL-10 is not only secreted by Th2, but also secreted by a subset of CD4 + T cells, including Th1 and Th17, B cells, neutrophil cells, and macrophages. 17 IL-10 is generally thought to modulate the ability of the immune response and allow bacterial elimination without damaging the host tissue, but in some cases the absence of IL-10 makes the immune response more eff ective in eliminating pathogens, but resulting in more damage to the tissue and aff ects the survival of the host. 20,21 The mean level of IL-10 in pulmonary TB patients with RS and RR in this study were 128.81 ± 135.77 pg/ml and 125.15 ± 118.32 pg/ ml respectively.…”