Nutritional status positively impacts humoral immunity against its Mycobacterium tuberculosis, disease progression, and vaccine development

Abstract

Nutritional status contributes to the regulation of immune responses against pathogens, and malnutrition has been considered as a risk factor for tuberculosis (TB). Mycobacterium tuberculosis (Mtb), the causative agent of TB, can modulate host lipid metabolism and induce lipid accumulation in macrophages, where the bacilli adopt a dormant phenotype. In addition, serum lipid components play dual roles in the regulation of and protection from Mtb infection. We analyzed the relationship between nutritional status and the humoral immune response in TB patients. We found that serum HDL levels are positively correlated with the serum IgA specific for Mtb antigens. Analysis of the relationship between serum nutritional parameters and clinical parameters in TB patients showed that serum albumin and CRP levels were negatively correlated before treatment. We also observed reduced serum LDL levels in TB patients following treatment. These findings may provide insight into the role of serum lipids in host immune responses against Mtb infection. Furthermore, improving the nutritional status may enhance vaccination efficacy.

Fig 1. Comparison of IgG responses to Mtb antigens in active TB (ATB) patients before and after treatment.

The levels of serum IgG in ATB patients against 7 antigens (ESAT-6, CFP-10, MDP1, Ag85A, Acr, HBHA, and HrpA) before treatment (labeled as “Before”) and after treatment (“After”) were analyzed by ELISA. Data shown are the average of triplicate experiments. There were no statistical changes in the levels of serum IgG against TB antigens before and after treatment.

Fig 2. IgA responses to Mtb antigens.

The levels of serum IgA in ATB patients against 7 antigens (ESAT-6, CFP-10, MDP1, Ag85A, Acr, HBHA, and HrpA) before treatment (labeled as “Before”) and after treatment (“After”) were analyzed by ELISA. The results of the IgA-ELISA were expressed as ELISA-Index, as described in “Subjects and Methods”. Also, there were no significant differences in the levels of serum IgA against TB antigens before and after treatment.

Fig 3. The levels of serum IgG against HrpA before treatment in “Smear at entry”.

The levels of serum IgG against HrpA before treatment were compared to the severity in “Smear at entry” sub-grouped between 1+, 2+ and 3+. HrpA-IgG levels before treatment were found to have a positive relationship with “smear at entry” scores. **: p < 0.01.

Fig 4. Comparison of CRP and serum nutritional parameters.

(A) Correlation between serum CRP level and albumin in active TB patients before treatment. (B) The relationship between serum lipids and serum albumin levels in TB patients at the onset of treatment. (C) The relationship between serum CRP levels and nutritional parameters in TB patients after chemotherapy. (D) The relationship between serum lipid parameters and serum albumin levels in TB patients after chemotherapy.

Fig 5. Correlation between antibody levels and nutritional status before and after treatment.

(A) Correlation between serum HDL concentrations and serum IgA levels specific to Mtb antigens before TB treatment. (B) Correlation between serum total cholesterol levels and serum IgA levels specific to Mtb antigens before TB treatment.

Fig 6. Changes in serum nutritional status in ATB patients during treatment.

Analysis of serum nutritional levels showed a significant decrease in serum LDL levels in ATB patients after treatment. **: p < 0.01.