Epidemiologic Evidence of and Potential Mechanisms by Which Second-Hand Smoke Causes Predisposition to Latent and Active Tuberculosis

Xiyuan Bai,Shanae L. Aerts,Deepshikha Verma,Diane J. Ordway,Edward D. Chan 대한면역학회 2018 Immune Network Vol.18 No.3

Many studies have linked cigarette smoke (CS) exposure and tuberculosis (TB) infection and disease although much fewer have studied second-hand smoke (SHS) exposure. Our goal is to review the epidemiologic link between SHS and TB as well as to summarize the effects SHS and direct CS on various immune cells relevant for TB. PubMed searches were performed using the key words “tuberculosis” with “cigarette,” “tobacco,” or “second-hand smoke.” The bibliography of relevant papers were examined for additional relevant publications. Relatively few studies associate SHS exposure with TB infection and active disease. Both SHS and direct CS can alter various components of host immunity resulting in increased vulnerability to TB. While the epidemiologic link of these 2 health maladies is robust, more definitive, mechanistic studies are required to prove that SHS and direct CS actually cause increased susceptibility to TB.

Human IL-32 expression protects mice against a hypervirulent strain of <i>Mycobacterium tuberculosis</i>

Bai, Xiyuan,Shang, Shaobin,Henao-Tamayo, Marcela,Basaraba, Randall J.,Ovrutsky, Alida R.,Matsuda, Jennifer L.,Takeda, Katsuyuki,Chan, Mallory M.,Dakhama, Azzeddine,Kinney, William H.,Trostel, Jessica National Academy of Sciences 2015 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.112 No.16

<P><B>Significance</B></P><P>Interleukin-32 (IL-32) is induced by IL-1β, Toll-like receptor agonists, and nucleotide oligomerization domain as well as by <I>Mycobacterium tuberculosis</I> (<I>MTB</I>). Expression of human IL-32γ in the lungs of mice reduced the burden of <I>MTB</I> in both the lungs but also in the spleen and was associated with increased survival. Mechanistically, increased numbers of host-protective innate and adaptive immune cells were present in the IL-32 transgenic mice. Alveolar macrophages from the transgenic mice were also better able to control <I>MTB</I> infection and had increased colocalization of <I>MTB</I> with lysosomes. IL-32 expression was increased in the surgically resected lungs of tuberculosis patients, particularly in macrophages, airway epithelial cells, B cells, and T cells. Thus, IL-32 enhances host immunity against <I>MTB</I>.</P><P>Silencing of interleukin-32 (IL-32) in a differentiated human promonocytic cell line impairs killing of <I>Mycobacterium tuberculosis</I> (<I>MTB</I>) but the role of IL-32 in vivo against <I>MTB</I> remains unknown. To study the effects of IL-32 in vivo, a transgenic mouse was generated in which the human <I>IL-32γ</I> gene is expressed using the surfactant protein C promoter (SPC-IL-32γTg). Wild-type and SPC-IL-32γTg mice were infected with a low-dose aerosol of a hypervirulent strain of <I>MTB</I> (W-Beijing HN878). At 30 and 60 d after infection, the transgenic mice had 66% and 85% fewer <I>MTB</I> in the lungs and 49% and 68% fewer <I>MTB</I> in the spleens, respectively; the transgenic mice also exhibited greater survival. Increased numbers of host-protective innate and adaptive immune cells were present in SPC-IL-32γTg mice, including tumor necrosis factor-alpha (TNFα) positive lung macrophages and dendritic cells, and IFN-gamma (IFNγ) and TNFα positive CD4<SUP>+</SUP> and CD8<SUP>+</SUP> T cells in the lungs and mediastinal lymph nodes. Alveolar macrophages from transgenic mice infected with <I>MTB</I> ex vivo had reduced bacterial burden and increased colocalization of green fluorescent protein-labeled <I>MTB</I> with lysosomes. Furthermore, mouse macrophages made to express IL-32γ but not the splice variant IL-32β were better able to limit <I>MTB</I> growth than macrophages capable of producing both. The lungs of patients with tuberculosis showed increased IL-32 expression, particularly in macrophages of granulomas and airway epithelial cells but also B cells and T cells. We conclude that IL-32γ enhances host immunity to <I>MTB</I>.</P>

Characterization of Immune Cells From the Lungs of Patients With Chronic Non-Tuberculous Mycobacteria or Pseudomonas aeruginosa Infection

Schenkel Alan R.,Mitchell John D.,Cool Carlyne D.,Bai Xiyuan,Groshong Steve,Koelsch Tilman,Verma Deepshikha,Ordway Diane,Chan Edward D. 대한면역학회 2022 Immune Network Vol.22 No.3

Little is known of the lung cellular immunophenotypes in patients with non-tuberculous mycobacterial lung disease (NTM-LD). Flow-cytometric analyses for the major myeloid and lymphoid cell subsets were performed in less- and more-diseased areas of surgically resected lungs from six patients with NTM-LD and two with Pseudomonas aeruginosa lung disease (PsA-LD). Lymphocytes, comprised mainly of NK cells, CD4+ and CD8+ T cells, and B cells, accounted for ~60% of all leukocytes, with greater prevalence of T and B cells in more-diseased areas. In contrast, fewer neutrophils were found with decreased number in more-diseased areas. Compared to NTM-LD, lung tissues from patients with PsA-LD demonstrated relatively lower numbers of T and B lymphocytes but similar numbers of NK cells. While this study demonstrated a large influx of lymphocytes into the lungs of patients with chronic NTM-LD, further analyses of their phenotypes are necessary to determine the significance of these findings.

IL-32-induced Inflammatory Cytokines Are Selectively Suppressed by a1-antitrypsin in Mouse Bone Marrow Cells

이시영,최동기,곽아름,김시내,Tam Thanh Nguyen,길가애,김은혜,유광하,김인애,이영민,전현정,Edward D. Chan,Xiyuan Bai,김현우,김용성,김수현 대한면역학회 2017 Immune Network Vol.17 No.2

The induction of interleukin (IL)-32 in bone marrow (BM) inflammation is crucial in graft versus host disease (GvHD) that is a common side effect of allogeneic BM transplantation. Clinical trials on a-1 antitrypsin (AAT) in patients with GvHD are based on the preliminary human and mouse studies on AAT reducing the severity of GvHD. Proteinase 3 (PR3) is an IL-32-binding protein that was isolated from human urine. IL-32 primarily induces inflammatory cytokines in myeloid cells, probably due to PR3 expression on the membrane of the myeloid lineage cells. The inhibitory activity of AAT on serine proteinases may explain the anti-inflammatory effect of AAT on GvHD. However, the anti-inflammatory activity of AAT on BM cells remains unclear. Mouse BM cells were treated with IL-32g and different inflammatory stimuli to investigate the anti-inflammatory activity of AAT. Recombinant AATFc fusion protein inhibited IL-32g-induced IL-6 expression in BM cells, but failed to suppress that induced by other stimuli. In addition, the binding of IL-32g to PR3 was abrogated by AAT-Fc. The data suggest that the specific antiinflammatory effect of AAT in mouse BM cells is due to the blocking of IL-32 binding to membrane PR3.

IL-32-induced Inflammatory Cytokines Are Selectively Suppressed by α1-antitrypsin in Mouse Bone Marrow Cells

Lee, Siyoung,Choi, Dong-Ki,Kwak, Areum,Kim, Sinae,Nguyen, Tam Thanh,Gil, Gaae,Kim, Eunhye,Yoo, Kwang Ha,Kim, In Ae,Lee, Youngmin,Jhun, Hyunjhung,Chan, Edward D.,Bai, Xiyuan,Kim, Hyunwoo,Kim, Yong-Sung 한국조명·전기설비학회 2017 한국조명·전기설비학회 학술대회논문집 Vol. No.

<P>The induction of interleukin (IL)-32 in bone marrow (BM) inflammation is crucial in graft versus host disease (GvHD) that is a common side effect of allogeneic BM transplantation. Clinical trials on α-1 antitrypsin (AAT) in patients with GvHD are based on the preliminary human and mouse studies on AAT reducing the severity of GvHD. Proteinase 3 (PR3) is an IL-32-binding protein that was isolated from human urine. IL-32 primarily induces inflammatory cytokines in myeloid cells, probably due to PR3 expression on the membrane of the myeloid lineage cells. The inhibitory activity of AAT on serine proteinases may explain the anti-inflammatory effect of AAT on GvHD. However, the anti-inflammatory activity of AAT on BM cells remains unclear. Mouse BM cells were treated with IL-32γ and different inflammatory stimuli to investigate the anti-inflammatory activity of AAT. Recombinant AAT-Fc fusion protein inhibited IL-32γ-induced IL-6 expression in BM cells, but failed to suppress that induced by other stimuli. In addition, the binding of IL-32γ to PR3 was abrogated by AAT-Fc. The data suggest that the specific anti-inflammatory effect of AAT in mouse BM cells is due to the blocking of IL-32 binding to membrane PR3.</P>