The Goldilocks model of immune symbiosis with Mycobacteria and Candida colonizers

Abstract

Mycobacteria and Candida species include significant human pathogens that can cause localized or disseminated infections. Although these organisms may appear to have little in common, several shared pathways of immune recognition and response are important for both control and infection-related pathology. In this article, we compare and contrast the innate and adaptive components of the immune system that pertain to these infections in humans and animal models. We also explore a relatively new concept in the mycobacterial field: biological commensalism. Similar to the well-established model of Candida infection, Mycobacterial species colonize their human hosts in equilibrium with the immune response. Perturbations in the immune response permit the progression to pathologic disease at the expense of the host. Understanding the immune factors required to maintain commensalism may aid with the development of diagnostic and treatment strategies for both categories of pathogens.

Inhibition of IL‐17A by secukinumab shows no evidence of increased Mycobacterium tuberculosis infections

“…17 This suggests that infection susceptibility to extracellular fungi such as C. albicans is likely a result of a combination of factors rather than a deficiency of just one cytokine, a situation likely to apply as well for host resistance to intracellular pathogens such as M. tuberculosis. [19][20][21][22]61,64 In summary, the absence of TB reactivation in secukinumab clinical studies 17 (and further detailed here) is moreover supported by experimental in vitro studies showing lack of effect of secukinumab on M. tuberculosis dormancy in a human in vitro microgranuloma model (this study), and lack of compromised host resistance in anti-IL-17A-treated M. tuberculosis-infected mice. 37 Collecting real-world evidence data, through registries, will be an opportunity to further substantiate the safety of secukinumab in this regard.…”

“…61 TNFα, interferon-γ, IL-12p40 and IL-1α/IL-1β are of particular importance, 50,51,61 however, the role of IL-17A in different stages of host resistance to M. tuberculosis is more equivocal. [18][19][20][21][22] The IL-17 pathway seems to be dispensable for low-dose M. tuberculosis host resistance in mice infected with the commonly investigated M. tuberculosis strain H37Rv, 18,32 but, protective immunity to hypervirulent M. tuberculosis strain HN878 appears to be IL-17A-dependent in mice. 32 However, other predominantly intracellular cytokines such as IL-32γ, which occur in humans but not in rodents, 62 may be more important even against the hypervirulent M. tuberculosis strain HN878.…”

“…To date, no cases of reactivation of latent tuberculosis (TB) infection (LTBI) were observed. 17 However, reports that IL-17A-producing γδT cells and CD4 + T cells might have protective or pathologic roles during different phases of Mycobacterium tuberculosis infection 15,16,[18][19][20][21][22] emphasize the need to further explore the role of IL-17A in this context.…”

The Many Lives of Nontuberculous Mycobacteria

“…A genetic basis for the SM¡RM transition is the lost expression of genes that promote glycopeptidolipid (GPL) synthesis and transport (111,120). GPLs are amphiphilic molecules that localize to the outermost layer of the mycobacterial cell wall (1). GPL localization to the mycobacterial cell wall is facilitated by several genes, including mps1, mbtH, and mmpL4b (120).…”

“…This is especially true of children with NTMI, in whom disease manifests primarily as a distressful and disfiguring cervical lymphadenitis. It is important to have a basic understanding of the host and bacterial factors that maintain human-NTM commensalism, as their perturbation may cause an infection to progress at the expense of the human host (1).…”