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Coinfection with Leishmania major and Staphylococcus aureus enhances the pathologic responses to both microbes through a pathway involving IL-17A
Journal article   Open access

Coinfection with Leishmania major and Staphylococcus aureus enhances the pathologic responses to both microbes through a pathway involving IL-17A

Tiffany Y Borbón, Breanna M Scorza, Gwendolyn M Clay, Fellipe Lima Nobre de Queiroz, Alan J Sariol, Jayden L Bowen, Yani Chen, Bayan Zhanbolat, Corey P Parlet, Diogo G Valadares, …
PLoS neglected tropical diseases, Vol.13(5), pp.e0007247-e0007247
05/2019
DOI: 10.1371/journal.pntd.0007247
PMCID: PMC6527190
PMID: 31107882
url
https://doi.org/10.1371/journal.pntd.0007247View
Published (Version of record) Open Access

Abstract

Cutaneous leishmaniasis (CL) is a parasitic disease causing chronic, ulcerating skin lesions. Most humans infected with the causative Leishmania protozoa are asymptomatic. Leishmania spp. are usually introduced by sand flies into the dermis of mammalian hosts in the presence of bacteria from either the host skin, sand fly gut or both. We hypothesized that bacteria at the dermal inoculation site of Leishmania major will influence the severity of infection that ensues. A C57BL/6 mouse ear model of single or coinfection with Leishmania major, Staphylococcus aureus, or both showed that single pathogen infections caused localized lesions that peaked after 2-3 days for S. aureus and 3 weeks for L. major infection, but that coinfection produced lesions that were two-fold larger than single infection throughout 4 weeks after coinfection. Coinfection increased S. aureus burdens over 7 days, whereas L. major burdens (3, 7, 28 days) were the same in singly and coinfected ears. Inflammatory lesions throughout the first 4 weeks of coinfection had more neutrophils than did singly infected lesions, and the recruited neutrophils from early (day 1) lesions had similar phagocytic and NADPH oxidase capacities. However, most neutrophils were apoptotic, and transcription of immunomodulatory genes that promote efferocytosis was not upregulated, suggesting that the increased numbers of neutrophils may, in part, reflect defective clearance and resolution of the inflammatory response. In addition, the presence of more IL-17A-producing γδ and non-γδ T cells in early lesions (1-7 days), and L. major antigen-responsive Th17 cells after 28 days of coinfection, with a corresponding increase in IL-1β, may recruit more naïve neutrophils into the inflammatory site. Neutralization studies suggest that IL-17A contributed to an enhanced inflammatory response, whereas IL-1β has an important role in controlling bacterial replication. Taken together, these data suggest that coinfection of L. major infection with S. aureus exacerbates disease, both by promoting more inflammation and neutrophil recruitment and by increasing neutrophil apoptosis and delaying resolution of the inflammatory response. These data illustrate the profound impact that coinfecting microorganisms can exert on inflammatory lesion pathology and host adaptive immune responses.
 Staphylococcal Infections - pathology Staphylococcus aureus - physiology Humans Leishmania major - genetics Interleukin-17 - immunology Leishmania major - physiology Interleukin-1beta - genetics Coinfection - parasitology Leishmaniasis, Cutaneous - immunology Female Staphylococcal Infections - microbiology Leishmania major - isolation & purification Leishmaniasis, Cutaneous - genetics Staphylococcus aureus - genetics Staphylococcal Infections - genetics Staphylococcal Infections - immunology Staphylococcus aureus - isolation & purification Coinfection - immunology Mice, Inbred C57BL Leishmaniasis, Cutaneous - pathology Neutrophils - immunology Interleukin-17 - genetics Interleukin-1beta - immunology Coinfection - microbiology Animals Coinfection - pathology Leishmaniasis, Cutaneous - parasitology Th17 Cells - immunology Mice

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