Optimal clearance of Sporothrix schenckii requires an intact Th17 response in a mouse model of systemic infection

Ferreira, Lucas Souza; Gonçalves, Amanda; Portuondo, Deivys Leandro; Maia, Danielle Cardoso Geraldo; Placeres, Marisa Campos Polési; Batista-Duharte, Alexander; Carlos, Iracilda Zeppone

doi:10.1016/j.imbio.2015.02.009

Cited by 48 publications

(59 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…13 Also, skin-tissue-resident NK cells express lower levels of CD49b than splenic cNK cells, have constitutive CD69 expression, and are also mature CD11b + CD27 + cells. Although apparently not serving as an IFN-c source, as we had previously suggested, 52 and in a way mostly contrary to our initial expectations, NK cells proved to be an essential component of the immune machinery driving the elimination of S. schenckii. Our decision to use a model of systemic disease was aimed at gaining insight into the immune mechanisms engaged when this disease does become systemic, without having to resort to immunosuppression, which has also the added benefit of showing how NK cells respond in commonly used systemic experimental models.…”

Section: Discussioncontrasting

confidence: 99%

Natural killer cells are pivotal for in vivo protection following systemic infection by Sporothrix schenckii

et al. 2018

Self Cite

View full text Add to dashboard Cite

Natural killer (NK) cells are one of the first cell types to enter inflammation sites and have been historically known as key effector cells against tumours and viruses; now, accumulating evidence shows that NK cells are also capable of direct in vitro activity and play a protective role against clinically important fungi in vivo. However, our understanding of NK cell development, maturation and activation in the setting of fungal infections is preliminary at best. Sporotrichosis is an emerging worldwide-distributed subcutaneous mycosis endemic in many countries, affecting humans and other animals and caused by various related thermodimorphic Sporothrix species, whose prototypical member is Sporothrix schenckii. We show that following systemic infection of BALB/c mice with S. schenckii sensu stricto, NK cells displayed a more mature phenotype as early as 5 days post-infection as judged by CD11b/CD27 expression. At 10 days post-infection, NK cells had increased expression of CD62 ligand (CD62L) and killer cell lectin-like receptor subfamily G member 1 (KLRG1), but not of CD25 or CD69. Depletion of NK cells with anti-asialo GM1 drastically impaired fungal clearance, leading to a more than eightfold increase in splenic fungal load accompanied by heightened systemic inflammation, as shown by augmented production of the pro-inflammatory cytokines tumour necrosis factor-α, interferon-γ and interleukin-6, but not interleukin-17A, in the spleen and serum. Our study is, to the best of our knowledge, the first to demonstrate that a fungal infection can drive NK cell maturation in vivo and that such cells are pivotal for in vivo protection against S. schenckii.

show abstract

Section: Discussioncontrasting

confidence: 99%

Natural killer cells are pivotal for in vivo protection following systemic infection by Sporothrix schenckii

et al. 2018

Self Cite

View full text Add to dashboard Cite

show abstract

“…A low frequency of both cell types and a diminished release of IL‐17 were found in all three KO groups albeit with important timing differences, suggesting that the S. schenckii infection stage determines the requirement of the Th17 response for NLRP3‐triggered mechanisms. Our findings lead us to believe that the inflammasome‐derived mechanisms involved in controlling the S. schenckii infection are probably linked to the Th17 response, which is in accordance with the recently reported protective role of such a response in this infection . Furthermore, it seems that the inflammasome‐induced development of the Th17 response in our model is partially due to its effect on IL‐1 β .…”

Section: Discussionsupporting

confidence: 92%

“…Previous studies showed that cell‐based and innate immune responses are developed during the S. schenckii infection in mice and that T helper type 1 (Th1) and Th2 responses are elicited in an antigen‐specific manner against cell‐wall antigens of this fungus . More recently, we showed that S. schenckii systemic mouse infection induces the development of a protective Th17 response, featuring both Th17 and Th17/Th1 cells and the augmented ex vivo release of interleukin‐17 (IL‐17) and IL‐22 . We also showed that the passive transference of sera from mice immunized with Al(OH) 3 ‐adjuvanted S. schenckii cell‐wall proteins can induce protection in a subsequent challenge with the fungus …”

Section: Introductionmentioning

confidence: 85%

The NLRP3 inflammasome contributes to host protection during Sporothrix schenckii infection

et al. 2017

Self Cite

View full text Add to dashboard Cite

Sporotrichosis is a mycosis caused by fungi from the Sporothrix schenckii species complex, whose prototypical member is Sporothrix schenckii sensu stricto. Pattern recognition receptors (PRRs) recognize and respond to pathogen-associated molecular patterns (PAMPs) and shape the following adaptive immune response. A family of PRRs most frequently associated with fungal recognition is the nucleotide-binding oligomerization domain-like receptor (NLR). After PAMP recognition, NLR family pyrin domain-containing 3 (NLRP3) binds to apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and caspase-1 to form the NLRP3 inflammasome. When activated, this complex promotes the maturation of the pro-inflammatory cytokines interleukin-1β (IL-1β) and IL-18 and cell death through pyroptosis. In this study, we aimed to evaluate the importance of the NLRP3 inflammasome in the outcome of S. schenckii infection using the following three different knockout (KO) mice: NLRP3 , ASC and caspase-1 . All KO mice were more susceptible to infection than the wild-type, suggesting that NLRP3-triggered responses contribute to host protection during S. schenckii infection. Furthermore, the NLRP3 inflammasome appeared to be critical for the ex vivo release of IL-1β, IL-18 and IL-17 but not interferon-γ. Additionally, a role for the inflammasome in shaping the adaptive immune response was suggested by the lower frequencies of type 17 helper T (Th17) cells and Th1/Th17 but not Th1 cells in S. schenckii-infected KO mice. Overall, our results indicate that the NLRP3 inflammasome links the innate recognition of S. schenckii to the adaptive immune response, so contributing to protection against this infection.

show abstract

“…From the eight cats in this study, two (cases C and S) were FIV positive and one of these (case S) was cured after 12 months of treatment (data not shown), whereas none were FeLV positive. Understanding of the immunological processes in Sporothrix infection in cats is limited, although the role of an intact and capable Th1 and Th17 cellular response has been documented in cats and mice …”

Section: Discussionmentioning

confidence: 99%

Comparison of two in vitro antifungal sensitivity tests and monitoring during therapy of Sporothrix schenckii sensu stricto in Malaysian cats

Han¹,

Kano

Chen

et al. 2017

Veterinary Dermatology

View full text Add to dashboard Cite

show abstract

Optimal clearance of Sporothrix schenckii requires an intact Th17 response in a mouse model of systemic infection

Cited by 48 publications

References 46 publications

Natural killer cells are pivotal for in vivo protection following systemic infection by Sporothrix schenckii

Natural killer cells are pivotal for in vivo protection following systemic infection by Sporothrix schenckii

The NLRP3 inflammasome contributes to host protection during Sporothrix schenckii infection

Comparison of two in vitro antifungal sensitivity tests and monitoring during therapy of Sporothrix schenckii sensu stricto in Malaysian cats

Contact Info

Product

Resources

About