One Episode of Self-Resolving Plasmodium yoelii Infection Transiently Exacerbates Chronic Mycobacterium tuberculosis Infection

Abstract

Malaria and tuberculosis (Tb) are two of the main causes of death from infectious diseases globally. The pathogenic agents, Plasmodium parasites and Mycobacterium tuberculosis, are co-endemic in many regions in the world, however, compared to other co-infections like HIV/Tb or helminth/Tb, malaria/Tb has been given less attention both in clinical and immunological studies. Due to the lack of sufficient human data, the impact of malaria on Tb and vice versa is difficult to estimate but co-infections are likely to occur very frequently. Due to its immunomodulatory properties malaria might be an underestimated risk factor for latent or active Tb patients particularly in high-endemic malaria settings were people experience reinfections very frequently. In the present study, we used the non-lethal strain of Plasmodium yoelii to investigate, how one episode of self-resolving malaria impact on a chronic M. tuberculosis infection. P. yoelii co-infection resulted in exacerbation of Tb disease as demonstrated by increased pathology and cellular infiltration of the lungs which coincided with elevated levels of pro- and anti-inflammatory mediators. T cell responses were not impaired in co-infected mice but enhanced and likely contributed to increased cytokine production. We found a slight but statistically significant increase in M. tuberculosis burden in co-infected animals and increased lung CFU was positively correlated with elevated levels of TNFα but not IL-10. Infection with P. yoelii induced the recruitment of a CD11c+ population into lungs and spleens of M. tuberculosis infected mice. CD11c+ cells isolated from P. yoelii infected spleens promoted survival and growth of M. tuberculosis in vitro. 170 days after P. yoelii infection changes in immunopathology and cellular immune responses were no longer apparent while M. tuberculosis numbers were still slightly higher in lungs, but not in spleens of co-infected mice. In conclusion, one episode of P. yoelii co-infection transiently exacerbated disease severity but had no long-term consequences on disease progression and survival of M. tuberculosis infected mice.

Lessons Learned for Pathogenesis, Immunology, and Disease of Erythrocytic Parasites: Plasmodium and Babesia

“…Furthermore, increased B. burgdorferi burden in organs and severe inflammatory Lyme disease manifestations resulted due to immunosuppression by B. microti in coinfected mice showed an association with enhanced Lyme disease manifestations ( Djokic et al., 2019 ). A similar response was also reported with respect to Mycobacterium tuberculosis coinfection with rodent malaria parasite P. yoeli ( Blank et al., 2016 ).…”

Prevalence of Malaria and TB Coinfection at a National Tuberculosis Treatment Centre in Uganda

“…A malaria antigen rapid diagnostic test (RDT) (SD BIOLINE Malaria Ag P.f/Pan®) was performed only when the smear was negative. Using RDT is justifiable as the immune effects of malaria on TB may last up to 5 months after the malaria infection has cleared [30]. One was considered to have malaria if either a thick blood smear or a rapid diagnostic test was positive.…”

Increased male susceptibility to Mycobacterium tuberculosis infection is associated with smaller B cell follicles in the lungs

“…Total RNA from lung tissue was extracted using TRIzol ® reagent (Invitrogen) as recommended by the manufacturer. For quantitative real-time PCR (qRT-PCR), 2000 ng of total RNA were reverse transcribed using Maxima First Strand cDNA Synthesis Kit for RT-qPCR (Thermo Fisher Scientific) as previously described 14 . Primer sequences are depicted in Table 1.…”