One-Two Punch: Cooperative Toll-Like Receptor 2 (TLR2) and Inflammasome (NLRP3) Recognition of Bacterial Amyloids
Production of mature interleukin 1β (IL-1β) is a two-step process. The first step begins with the generation of pro-IL-1β following an initial signal from a Toll-like receptor (TLR), while the second step involves the activation of inflammasome complexes leading to the activation of caspase 1, which cleaves pro-IL-1β to make mature IL-1β. IL-1β has been implicated in many debilitating amyloid-associated human diseases, including Alzheimer's and Parkinson's diseases. In addition to accumulating during human diseases, amyloids, proteins with a cross-beta-sheet quaternary structure, are produced in the extracellular matrix of many bacterial biofilms. Rapsinski et al. (p. 693–701) show that the enteric amyloid termed curli is recognized by both TLR2 and the NLRP3 inflammasome and that this dual receptor activation by curli leads to the generation of IL-1β. This new information provides potential insight into the immune modulation by amyloid-producing bacteria and amyloid-associated human diseases.
Correlation between Nasal Microbiome Composition and Remote Purulent Skin and Soft Tissue Infections
Nasal colonization with Staphylococcus aureus is an important risk factor for development of remote skin and soft tissue infections (SSTIs); however, it is unclear why some colonized individuals develop disease while others do not. Johnson et al. (p. 802–811) use high-throughput sequencing to characterize nasal and abscess microbiomes of military infantry stationed at Fort Benning, Georgia. Individuals with SSTIs have significant differences in nasal microbiome structure compared to that of healthy controls; additionally, they harbor a surprising number of polymicrobial abscesses. Together, these data indicate a correlation between nasal microbiome structure and SSTI development.
B Cells Provide Antigen-Independent Mechanisms To Protect On-Demand Hematopoiesis during Systemic Responses to Pneumocystis murina Lung Infection
HIV infection results in complex immunodeficiencies affecting CD4+ T cell, type I interferon (IFN), and B cell functions, allowing Pneumocystis murina pneumonia and unexplained comorbidities, including progressive bone marrow dysfunctions. B cells provide critical support for on-demand hematopoiesis following Pneumocystis infection, a process otherwise hampered by systemic innate immune effects initiated by a defective type I IFN system. Hoyt et al. (p. 743–758) demonstrate that B cells specifically protect hematopoietic progenitor activity by mechanisms involving induction of interleukin-10 (IL-10) and IL-27 in accessory, likely dendritic-type, cells. Thus, B cells complement the immune modulatory role of type I IFNs to prevent systemic complications during Pneumocystis infection.
Protection from Candida albicans Infection through Inactivation of the Sts Phosphatases
The fungal pathogen Candida albicans causes lethal systemic infections that lead to widespread inflammatory damage and organ failure. To investigate host factors that regulate the immune response to infection, Naseem et al. (p. 637–645) evaluated mice lacking the immunomodulatory Sts proteins and found them to be resistant to C. albicans infection. Pathogen clearance in these mutant mice was followed by decreased levels of many inflammatory markers shortly after infection. Overall, mutant mice cleared and survived a lethal dose of C. albicans without the organ damage evident in wild-type mice. These results suggest new opportunities to optimize host immune responses toward this common pathogen.
bis-Molybdopterin Guanine Dinucleotide Is Required for Persistence of Mycobacterium tuberculosis
A critical feature of Mycobacterium tuberculosis pathogenesis is the ability to survive and proliferate under hypoxic conditions within granulomatous lesions in human pulmonary tuberculosis (TB). Williams et al. (p. 544–550) show that the bis-molybdopterin guanine dinucleotide (bis-MGD) form of molybdenum cofactor is essential for persistence of M. tuberculosis in the hypoxic granulomas of infected guinea pigs, which recapitulate pathological features of human TB disease. In contrast, bis-MGD is dispensable for growth and survival of M. tuberculosis in the murine TB infection model, where pulmonary lesions are not hypoxic. This work supports an important role for molybdenum cofactors in TB disease.
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- One-Two Punch: Cooperative Toll-Like Receptor 2 (TLR2) and Inflammasome (NLRP3) Recognition of Bacterial Amyloids
- Correlation between Nasal Microbiome Composition and Remote Purulent Skin and Soft Tissue Infections
- B Cells Provide Antigen-Independent Mechanisms To Protect On-Demand Hematopoiesis during Systemic Responses to Pneumocystis murina Lung Infection
- Protection from Candida albicans Infection through Inactivation of the Sts Phosphatases
- bis-Molybdopterin Guanine Dinucleotide Is Required for Persistence of Mycobacterium tuberculosis
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