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IL-10 Part 3: IL-10 In Bacterial Infection Clearance Varies By Bacteria Type; MRSA Infections (Mold Colonization)

This article is not medical or healthcare advice. Before starting any medical or health related regimen, seek the advice of your Primary Care Physician or an M.D.


IL-10 Production Helps Survival or Hurts Survival Depending On Bacteria Type

"We conclude that IL-10 production is required for host survival during infections caused by extracellular and/or highly pro-inflammatory bacteria, including Streptococcus pneumoniae, Pseudomonas aeruginosa, Francisella tularensis, Escherichia coli, and Mycobacterium tuberculosis. On the other hand, IL-10 production impairs host survival during infections caused by intracellular bacteria or bacterial pathogens that modulate the inflammatory response, such as Klebsiella pneumoniae, Bordetella pertussis, Listeria monocytogenes, Brucella abortus and Salmonella enterica serovar Typhimurium."[1]


MRSA Infections - IL-10 Varies : Systemic Infection (Colonization) or Sub Cutaneous (Implant)

"During a MRSA (USA300) infection there is a rapid production of IL-10. The contribution of this cytokine for host survival varies according to the nature of the infection. During an acute systemic infection, the production of IL-10 by CD19+CDB220+ cells was required to control the bacterial dissemination and its production is associated with host survival . However, in a sub-cutaneous infection model, IL-10 produced mostly by MDSCs in the local wound impairs MRSA clearance, without affecting host survival. MRSA infects orthopedic devices. In this case, the production of IL-10 by MDSCs favors the biofilm formation on the surface of these devices inducing persistent infections that do not affect host mortality."[1]


"Since the MDR-bacteria and non-MDR bacteria present different virulence, it is possible to hypothesize that MDR-bacteria induce differential amounts of IL-10 during infection. Indeed, several studies corroborate this hypothesis. For example, ICU patients infected with extensively drug-resistant (XDR) P. aeruginosa presented elevated amounts of IL-10 in blood, as compared to patients infected with non-MDR P. aeruginosa. Same result was obtained in a mouse model of P. aeruginosa pneumonia. Consistently, patients infected with MDR M. tuberculosis presented higher amounts of IL-10 in the serum, as compared to patients infected with non-MDR M. tuberculosis. However, another group did not find any difference in IL-10 production in patients infected with MDR or non-MDR M. tuberculosis. Moreover, during a Staph. aureus endocarditis model, rabbits infected with MRSA presented higher amounts of IL-10 as compared to those infected with Methicillin susceptible S. aureus in the serum."[1]


"All these data suggest that MDR-bacteria might induce more IL-10 production than non-MDR bacteria. The only exception was found in A. baumannii infection, where children infected either with MDR A. baumannii presented the same levels of IL-10 as compared with children infected with non-MDR A. baumannii."[1]


"The next question then is as to how MDR-bacteria induce higher levels of IL-10. It is well known that antibiotic resistance not only involves the acquisition of hydrolytic enzymes, but also includes changes in proteins structure or expression of genes involved in virulence such as porins, two-component systems and others . Polysaccharide capsule, present in bacteria such as K. pneumoniae, P. aeruginosa, A. baumannii, S. aureus, among other bacteria, is an important determinant for antimicrobial peptides and Polymyxin B resistance . An increased ability to produce capsule may be an adaptation against antibiotics. Interestingly, capsule recognition by pattern recognition receptors (PRRs) triggers IL-10 production in myeloid cells . MgrB is an important regulator of gene expression in K. pneumoniae, deletion of mgrB increases the resistance to collistin and Polymyxin B by the remodeling of lipid A mediated by the PhoPQ system. This increased resistance is associated with increased virulence and reduced TNF-α production.  It is unknown whether LPS modification by MDR-bacteria leads to higher production of IL-10. This possibility is highly probable, given that LPS recognition by TLR4 induces IL-10 production in myeloid cells."[1]


"Multi-drug resistant N. gonorrhoeae carries the OPA gene. OPA inhibits the proliferation of CD4+ T cells and B cells , increases the expression of PD-L1 and stimulates the production of IL-10.

Even though the treatments against MDR bacteria are limited, they mostly consist of antibiotic administration. A recent report describe that Clarithromycin promotes the recruitment of anti-inflammatory myeloid cells able to produce IL-10, Arginase-1 and iNOS to the lung tissue and the spleen. The recruitment of these cells to the lung protects the host during pneumococcal pneumonia and in LPS endotoxin shock. It is unknown whether other antibiotics also induce the production of IL-10 or other anti-inflammatory mediators. This would be an interesting hypothesis to evaluate ."[1]


Conclusion MDR Bacteria / IL-10

"In the last years, increasing data support the idea that IL-10 production drives the development of a successful immune response during bacterial infection. However, whether IL-10 production is beneficial or not for host survival depends on the pathogen nature and the immune response associated to the infection.

For non-MDR bacterial infection IL-10 production is required for host survival during infections caused by extracellular and/or highly pro-inflammatory bacteria. Conversely, for MDR bacterial infection, IL-10 impairs host survival and bacterial clearance during intracellular and/or weak pro-inflammatory bacteria. During A. baumannii and MRSA infection, the production of IL-10 is required for host survival. Both bacteria have acquired different virulence factors that allow them to neutralize the host immune response at different stages. In this scenario, a hyperactive immune response may occur, being IL-10 essential to modulate the intensity of it."[1]


"Finally, it is quite interesting MDR-bacteria stimulates higher IL-10 production as compared with non-MDR bacteria. We believe that the differential production of IL-10 may be a consequence of the changed expression pattern of different virulence factors displayed by these bacteria. This fact could explain why in general these bacteria are less virulent and why higher bacterial dose are commonly used to study host–pathogen interaction in mice."[1]


References:

  1. Expanding the Current Knowledge About the Role of Interleukin-10 to Major Concerning Bacteria. By Hernán F. Peñaloza1 Loreani P. Noguera. Front. Microbiol., 18 September 2018

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