Helminth-induced arginase-1 exacerbates lung inflammation and disease severity in tuberculosis

Monin, Leticia; Griffiths, Kristin; Lam, Wing Y.; Gopal, Radha; Kang, Dongwan; Ahmed, Mushtaq; Ray, Anuradha; Cruz‐Lagunas, Alfredo; Zúñiga, Joaquı́n; Babu, Subash; Kolls, Jay K.; Mitreva, Makedonka; Rosa, Bruce A.; Ramos-Payán, Rosalío; Morrison, Thomas E.; Murray, Peter J.; Rangel-Moreno, Javier; Pearce, Edward J.; Khader, Shabaana A.

doi:10.1172/jci77378

Cited by 92 publications

(102 citation statements)

References 39 publications

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“…Finally, S. stercoralis infection is also known to influence the systemic responses of cytokines, including type 1, type 2, and type 17 cytokines, and other proinflammatory responses in coinfected individuals (10). The mechanism by which helminths drive this modulation is still not clearly understood, although the induction of alternatively activated macrophages and arginase-1 appears to play an important role (22,23).…”

Section: Discussionmentioning

confidence: 99%

Anthelmintic Therapy Modifies the Systemic and Mycobacterial Antigen-Stimulated Cytokine Profile in Helminth-Latent Mycobacterium tuberculosis Coinfection

et al. 2017

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Helminth infections are known to modulate cytokine responses in latent tuberculosis (LTB). However, very few studies have examined whether this modulation is reversible upon anthelmintic therapy. We measured the systemic and mycobacterial (TB) antigen-stimulated levels of type 1, type 2, type 17, and regulatory cytokines in individuals with LTB and with or without coexistent Strongyloides stercoralis infection before and after anthelmintic therapy. Our data reveal that individuals with LTB and coexistent S. stercoralis infection have significantly lower levels of systemic and TB antigen-stimulated type 1 (gamma interferon [IFN-␥], tumor necrosis factor alpha [TNF-␣], and interleukin-2 [IL-2]) and type 17 (IL-17A and/or IL-17F) cytokines and significantly higher levels of systemic but not TB antigen-stimulated type 2 (IL-4 and IL-5) and regulatory (transforming growth factor beta [TGF-␤]) cytokines. Anthelmintic therapy resulted in significantly increased systemic levels of type 1 and/or type 17 cytokines and in significantly decreased systemic levels of type 2 and regulatory (IL-10 and TGF-␤) cytokines. In addition, anthelmintic therapy resulted in significantly increased TB antigen-stimulated levels of type 1 cytokines only. Our data therefore confirm that the modulation of systemic and TB antigen-stimulated cytokine responses in S. stercoralis-LTB coinfection is reversible (for the most part) by anthelmintic treatment.

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Section: Discussionmentioning

confidence: 99%

Anthelmintic Therapy Modifies the Systemic and Mycobacterial Antigen-Stimulated Cytokine Profile in Helminth-Latent Mycobacterium tuberculosis Coinfection

et al. 2017

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“…The third mechanism at play is a direct effect on T cells with decreased Th17 responses and increased expression of CTLA-4 [83]. Finally, the expression of arginase-1 during co-infections has been shown to mediate impaired Th1 responses to Mtb antigens and exacerbated pulmonary pathology [88]. Thus, animal models exploring the mechanisms underlying immune interactions in co-infection clearly reveal the complexity of this process.…”

Section: Helminth - Tuberculosis Co-infectionmentioning

confidence: 99%

Helminth-Tuberculosis Co-infection: An Immunologic Perspective

Babu

Nutman

2016

Trends in Immunology

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Over 2 billion people worldwide are infected with helminths (worms). Similarly, infection with Mycobacterium tuberculosis (Mtb) occurs in over a third of the world's population, often with a great degree of geographical overlap with helminth infection. Interestingly, the responses induced by the extracellular helminths and those induced by the intracellular Mtb are often mutually antagonistic and, as a consequence, can result in impaired (or cross-regulated) host responses to either of the infecting pathogens. In this review, we outline the nature of the immune responses induced by infections with helminths and tuberculosis (TB) and then provide data from both experimental models and human studies that illustrate how the immune response engendered by helminth parasites modulates Mtb-specific responses in helminth-TB co-infection.

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“…In addition, mRNA expression of genes associated with regulation, recruitment, and function of MDSCs such as Cxcl2, S100a8, S100a9, Arg1, Csf3, and Il11 was also higher in lungs of anti-IL-17-treated HN878-infected mice ( Figure 3I and Supplemental Table 1). mRNA gene expression associated with inflammation and lung damage such as albumin, Il1a, Il1b, serum amyloid proteins (SAA), matrix metalloproteases (MMPs), Ccl-chemokines, and collagenase (27) were also highly expressed in lungs of anti-IL-17-treated HN878-infected mice when compared with levels in isotypetreated HN878-infected mice. Furthermore, mRNA for Cxcl2, a key MDSC-recruiting chemokine (24), was highly expressed and localized within lungs of HN878-infected mice undergoing IL-17 neutralization, when compared with isotype-treated HN878-infected lungs ( Figure 3J).…”

Section: Il-17 Neutralization Leads To Mdsc Accumulation and Decreasementioning

confidence: 99%

“…Lung lobes were instilled with 10% neutral buffered formalin, embedded in paraffin, and processed as previously described (27). Endogenous biotin was neutralized by adding avidin, followed by incubation with biotin (both Sigma-Aldrich).…”

Section: Immunohistochemistrymentioning

confidence: 99%

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Interleukin-17 limits hypoxia-inducible factor 1α and development of hypoxic granulomas during tuberculosis

Domingo-Gonzalez¹,

Das²,

Griffiths³

et al. 2017

JCI Insight

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Helminth-induced arginase-1 exacerbates lung inflammation and disease severity in tuberculosis

Cited by 92 publications

References 39 publications

Anthelmintic Therapy Modifies the Systemic and Mycobacterial Antigen-Stimulated Cytokine Profile in Helminth-Latent Mycobacterium tuberculosis Coinfection

Anthelmintic Therapy Modifies the Systemic and Mycobacterial Antigen-Stimulated Cytokine Profile in Helminth-Latent Mycobacterium tuberculosis Coinfection

Helminth-Tuberculosis Co-infection: An Immunologic Perspective

Interleukin-17 limits hypoxia-inducible factor 1α and development of hypoxic granulomas during tuberculosis

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